Comparison of a Short Versus Long Stokes Shift Near-Infrared Dye During Intraoperative Molecular Imaging

Corbett, Christopher; Sulyok, Lydia G. Frenzel; Predina, Jarrod D.; Newton, Andrew D.; Bryski, Mitchell G.; Xia, Leilei; Stadanlick, Jason; Shin, Michael; Mahalingam, Sakkarapalayam M.; Singhal, Sunil

doi:10.1007/s11307-019-01434-2

Cited by 6 publications

(8 citation statements)

References 24 publications

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“…2 and S18). However, the standard deviation demonstrates heterogenous expression of FRα in both Skov-3 and A549 xenografts, as already demonstrated for other models [28] (Fig. 2a and 4c).…”

Section: Targeting Ligand Specificity and Ex Vivo Biodistributionsupporting

confidence: 79%

“…Such differences in physicochemical properties of the NIR fluorophores also have a major impact on the target binding specificity of their conjugates since, e.g. biodistribution and clearance can be affected with several cases previously reported where the choice of fluorophore, or linker, affected the affinity of the targeting ligand to the molecular target of interest [26][27][28]. Those studies highlight the importance of reducing background signal, improving contrast during FLI by avoiding non-specific binding, improving stability and enhancing clearance from the body.…”

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confidence: 99%

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Comparison of Five Near-Infrared Fluorescent Folate Conjugates in an Ovarian Cancer Model

et al. 2021

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Purpose Fluorescence imaging (FLI) using targeted near-infrared (NIR) conjugates aids the detection of tumour lesions pre- and intraoperatively. The optimisation of tumour visualisation and contrast is essential and can be achieved through high tumour-specificity and low background signal. However, the choice of fluorophore is recognised to alter biodistribution and clearance of conjugates and is therefore a determining factor in the specificity of target binding. Although ZW800-1, IRDye® 800CW and ICG are the most commonly employed NIR fluorophores in clinical settings, the fluorophore with optimal in vivo characteristics has yet to be determined. Therefore, we aimed to characterise the impact the choice of fluorophore has on the biodistribution, specificity and contrast, by comparing five different NIR fluorophores conjugated to folate, in an ovarian cancer model. Procedures ZW800-1, ZW800-1 Forte, IRDye® 800CW, ICG-OSu and an in-house synthesised Cy7 derivative were conjugated to folate through an ethylenediamine linker resulting in conjugates 1–5, respectively. The optical properties of all conjugates were determined by spectroscopy, the specificity was assessed in vitro by flow cytometry and FLI, and the biodistribution was studied in vivo and ex vivo in a subcutaneous Skov-3 ovarian cancer model. Results We demonstrated time- and receptor-dependent binding of folate conjugates in vitro and in vivo. Healthy tissue clearance characteristics and tumour-specific signal varied between conjugates 1–5. ZW800-1 Forte (2) revealed the highest contrast in folate receptor alpha (FRα)-positive xenografts and showed statistically significant target specificity. While conjugates 1, 2 and 3 are renally cleared, hepatobiliary excretion and no or very low accumulation in tumours was observed for 4 and 5. Conclusions The choice of fluorophore has a significant impact on the biodistribution and tumour contrast. ZW800-1 Forte (2) exhibited the best properties of those tested, with significant specific fluorescence signal.

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Section: Targeting Ligand Specificity and Ex Vivo Biodistributionsupporting

confidence: 79%

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confidence: 99%

Comparison of Five Near-Infrared Fluorescent Folate Conjugates in an Ovarian Cancer Model

et al. 2021

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“…Other nanostructures such as SWCNTs, nanodiamonds, QDs and AuNPs show wide absorption spectra, starting from ultraviolet (UV) and stretching down to the NIR region, with emissions in the NIR-I or NIR-II window 68,78,80,111 . The substantial role of the Stokes shift is particularly evident when imaging deep tissues; generally, the lesion depth seems to have greater influence on the fluorescence of dyes with a small Stokes shift 112 . For fluorescence detection at the tissue surface, fluorophores with a small Stokes shift (<30 nm) but high brightness provide greater imaging contrast 112 .…”

Section: Broadening Stokes Shiftmentioning

confidence: 99%

“…The substantial role of the Stokes shift is particularly evident when imaging deep tissues; generally, the lesion depth seems to have greater influence on the fluorescence of dyes with a small Stokes shift 112 . For fluorescence detection at the tissue surface, fluorophores with a small Stokes shift (<30 nm) but high brightness provide greater imaging contrast 112 . On the contrary, whole-body or deep-tissue imaging requires fluorophores with large Stokes shifts (>100 nm) 113 .…”

Section: Broadening Stokes Shiftmentioning

confidence: 99%

Near-infrared luminescence high-contrast in vivo biomedical imaging

2023

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Luminescence imaging in biomedical research has allowed new insights into the architecture of pathological tissues, signalling networks and cell interactions, and is now turning into a powerful tool for diagnostics and image-guided surgery. Luminescence in the near-infrared (NIR) window (700-1,700 nm), in particular, exhibits less interaction of scattering and absorption photons with biological tissues than imaging in the visible range, resulting in deeper optical penetration depth and reduced autofluorescence interference, and thus enabling higher imaging contrast. Despite promising preclinical results, few NIR fluorophores have been clinically approved so far. In this Review, we discuss important engineering challenges that need to be addressed to enable successful clinical translation of NIR luminescence imaging, including enhancement of imaging contrast by optimizing fluorescent probe design, reducing tissue autofluorescence and improving local accumulation of the luminescent probes in the body. Sections Key points• Luminescence imaging has revolutionized fundamental studies in life sciences, and its clinical application has allowed new insights into diagnostics and image-guided surgery.• Luminescence imaging with high contrast enables faster, safer, easier, more precise and less expensive clinical testing than positron emission tomography or computed tomography.• Luminescence in the near-infrared window benefits from minimal photon scattering/autofluorescence in biological tissues, enabling deep optical penetration and high imaging contrast.• The imaging contrast can be further improved by optimizing fluorophore performance (wavelength, brightness and Stokes shift), increasing fluorophore accumulation at target sites or reducing tissue background.• Although luminescence imaging shows great preclinical promise, its clinical application has been limited. A multidisciplinary effort for optimizing fluorophores, instruments, imaging and manufacturing standards is needed.Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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“…9,[14][15][16]18 Although the NIR fluorescence signal has depth limitations, it is a feasible intraoperative technique to provide a rapid intraoperative diagnosis, significantly decrease the total operative time, decrease the rate of conversion to open procedures, and allow for more complete removal of tumors, which has been demonstrated by intravenously injected ICG. 9,13,14,17,34,38,39,42 In addition, compared with other soft tissues, such as skin and liver, the lungs undergo volumetric changes through respiratory movements. Thus, the tumor depth in the collapsed lung during surgery was much less than that measured from preoperative chest In healthy lung tissue, inhaled ICG was distributed into the alveoli and phagocytized by alveolar macrophages.…”

Section: Limitationsmentioning

confidence: 99%

Evaluation of Intraoperative Near-Infrared Fluorescence Visualization of the Lung Tumor Margin With Indocyanine Green Inhalation

Jung

et al. 2020

JAMA Surg

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Identification of the tumor margin during surgery is important for precise minimal resection of lung tumors. Intravenous injection of indocyanine green (ICG) has several limitations when used for intraoperative visualization of lung cancer.OBJECTIVES To describe a technique for intraoperative visualization of lung tumor margin using ICG inhalation and evaluate the clinical applicability of the technique in mouse and rabbit lung tumor models as well as lung specimens of patients with lung tumors. DESIGN, SETTING, AND PARTICIPANTSIn lung tumor models of both mice and rabbits, the distribution of inhaled ICG in the lung tumor margin was investigated in vivo and ex vivo using a near-infrared imaging system. Lung tumor margin detection via inhalation of ICG was evaluated by comparing the results obtained with those of the intravenous injection method (n = 32, each time point for 4 mice). Based on preclinical data, use of ICG inhalation to help detect the tumor margin in patients with lung cancer was also evaluated (n = 6). This diagnostic study was conducted from May 31, 2017, to March 30, 2019. MAIN OUTCOMES AND MEASURESThe use of tumor margin detection by inhaled ICG was evaluated by comparing the inhaled formulation with intravenous administration of ICG. RESULTSFrom 10 minutes after inhalation of ICG to 24 hours, the distribution of ICG in the lungs was significantly higher than that in other organs (signal to noise ratio in the lungs: 39 486.4; interquartile range [IQR], 36 983.74-43 592.5). Ex vivo and histologic analysis showed that, in both lung tumor models, inhaled ICG was observed throughout the healthy lung tissue but was rarely found in tumor tissue. The difference in the fluorescent signal between healthy and tumor lung tissues was associated with the mechanical airway obstruction caused by the tumor and with alveolar macrophage uptake of the inhaled ICG in healthy tissues. Inhalation at a 20-fold lower dose of ICG had a 2-fold higher efficiency for tumor margin detection than did the intravenous injection (2.9; IQR, 2.7-3.2; P < .001). CONCLUSIONS AND RELEVANCEThe results of this study suggest that lung-specific inhalation delivery of ICG is feasible and may be useful for the intraoperative visualization of lung tumor margin in clinical practice.

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Comparison of a Short Versus Long Stokes Shift Near-Infrared Dye During Intraoperative Molecular Imaging

Cited by 6 publications

References 24 publications

Comparison of Five Near-Infrared Fluorescent Folate Conjugates in an Ovarian Cancer Model

Comparison of Five Near-Infrared Fluorescent Folate Conjugates in an Ovarian Cancer Model

Near-infrared luminescence high-contrast in vivo biomedical imaging

Evaluation of Intraoperative Near-Infrared Fluorescence Visualization of the Lung Tumor Margin With Indocyanine Green Inhalation

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