Fluorescent Lectins for Local in Vivo Visualization of Peripheral Nerves

KleinJan, G.H.; Buckle, Tessa; Willigen, Danny M. van; Oosterom, Matthias N. van; Spa, Silvia J.; Kloosterboer, Harmen Egbert; Leeuwen, Fijs W. B. van

doi:10.3390/molecules19079876

Cited by 16 publications

(11 citation statements)

References 44 publications

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“…Lectins are glycoproteins that bind to specific sugar residues (oligosaccharides) and have been developed to detect cell-surface glycans that are altered in cancer [ 90 , 109 ]. Unlike other posttranslational modifications, glycosylation is highly specific in cancer and provides a promising biomarker for early cancer detection [ 110 , 111 ]. Wheat germ agglutinin (WGA) is a lectin that has been fluorescein-labeled and topically administered to the epithelial surface of freshly resected specimens of whole human esophagus.…”

Section: Targeted Optical Imaging Agentsmentioning

confidence: 99%

“…(b) Immunofluorescence of human colon, including (HP), low-grade dysplasia (LGD), high grade dysplasia (HGD), and adenocarcinoma (AC), is shown stained with lectin Helix pomatia agglutinin (HPA) labeled with AF647. (c) Corresponding histology (H&E) ((a) reprinted and modified with the permission from [ 111 ] and (b) reprinted with the permission from [ 90 ]).…”

Section: Figurementioning

confidence: 99%

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Targeted Optical Imaging Agents in Cancer: Focus on Clinical Applications

Joshi

Wang

2018

Contrast Media & Molecular Imaging

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Molecular imaging is an emerging strategy for in vivo visualization of cancer over time based on biological mechanisms of disease activity. Optical imaging methods offer a number of advantages for real-time cancer detection, particularly in the epithelium of hollow organs and ducts, by using a broad spectral range of light that spans from visible to near-infrared. Targeted ligands are being developed for improved molecular specificity. These platforms include small molecule, peptide, affibody, activatable probes, lectin, and antibody. Fluorescence labeling is used to provide high image contrast. This emerging methodology is clinically useful for early cancer detection by identifying and localizing suspicious lesions that may not otherwise be seen and serves as a guide for tissue biopsy and surgical resection. Visualizing molecular expression patterns may also be useful to determine the best choice of therapy and to monitor efficacy. A number of these imaging agents are overcoming key challenges for clinical translation and are being validated in vivo for a wide range of human cancers.

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Section: Targeted Optical Imaging Agentsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Targeted Optical Imaging Agents in Cancer: Focus on Clinical Applications

Joshi

Wang

2018

Contrast Media & Molecular Imaging

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“…in head and neck cancers or prostate cancer), highlighting these vital structures could improve the surgeon's ability to avoid or preserve them. Thus far, direct visualization of nerves with fluorescent agents remains limited to a few preclinically tested nervebinding fluorophores, fluorescent peptides, and antibodies [33][34]. Color-coding tumors and critical structures for simultaneous viewing will require multi-spectral imaging.…”

Section: Fluorescence-guided Surgerymentioning

confidence: 99%

Emerging Intraoperative Imaging Modalities to Improve Surgical Precision

et al. 2018

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Intraoperative imaging (IOI) is performed to guide delineation and localization of regions of surgical interest. While oncological surgical planning predominantly utilizes x-ray computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US), intraoperative guidance mainly remains on surgeon interpretation and pathology for confirmation. Over the past decades however, intraoperative guidance has evolved significantly with the emergence of several novel imaging technologies, including fluorescence-, Raman, photoacoustic-, and radio-guided approaches. These modalities have demonstrated the potential to further optimize precision in surgical resection and improve clinical outcomes for patients. Not only can these technologies enhance our understanding of the disease, they can also yield large imaging datasets intraoperatively that can be analyzed by deep learning approaches for more rapid and accurate pathological diagnosis. Unfortunately, many of these novel technologies are still under preclinical or early clinical evaluation. Organizations like the Intra-Operative Imaging Study Group of the European Society for Molecular Imaging (ESMI) support interdisciplinary interactions with the aim to improve technical capabilities in the field, an approach that can succeed only if scientists, engineers, and physicians work closely together with industry and regulatory bodies to resolve roadblocks to clinical translation. In this review, we provide an overview of a variety of novel IOI technologies, discuss their challenges, and present future perspectives on the enormous potential of IOI for oncological surgical navigation.

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“…Human studies using local tracer administration have even demonstrated that fluorescence guidance can be connected with micro-dosing 5 . Alternatively, it has been argued that the up-and-coming concept of nerve imaging can benefit from approaches that rely on local administration to increase the effective local concentration 11 and to minimize the chance of systemic toxic side-effects 12 .…”

Section: Introductionmentioning

confidence: 99%

Fluorescence background quenching as a means to increase Signal to Background ratio - a proof of concept during Nerve Imaging

Buckle¹,

Wal²,

Willigen³

et al. 2020

Theranostics

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Introduction: Adequate signal to background ratios are critical for the implementation of fluorescence-guided surgery technologies. While local tracer administrations help to reduce the chance of systemic side effects, reduced spatial migration and non-specific tracer diffusion can impair the discrimination between the tissue of interest and the background. To combat background signals associated with local tracer administration, we explored a pretargeting concept aimed at quenching non-specific fluorescence signals. The efficacy of this concept was evaluated in an in vivo neuronal tracing set-up. Methods: Neuronal tracing was achieved using a wheat germ agglutinin (WGA) lectin . functionalized with an azide-containing Cy5 dye ( N 3 -Cy5-WGA ). A Cy7 quencher dye ( Cy7-DBCO ) was subsequently used to yield Cy7-Cy5-WGA , a compound wherein the Cy5 emission is quenched by Förster resonance energy transfer to Cy7. The photophysical properties of N 3 -Cy5-WGA and Cy7-Cy5-WGA were evaluated together with deactivation kinetics in situ, in vitro (Schwannoma cell culture) , ex vivo (muscle tissue from mice; used for dose optimization), and in vivo ( nervus ischiadicus in THY-1 YFP mice) . Results: In situ , conjugation of Cy7-DBCO to N 3 -Cy5-WGA resulted in >90% reduction of the Cy5 fluorescence signal intensity at 30 minutes after addition of the quencher. In cells, pretargeting with the N 3 -Cy5-WGA lectin yielded membranous staining, which could efficiently be deactivated by Cy7-DBCO over the course of 30 minutes (91% Cy5 signal decrease). In ex vivo muscle tissue, administration of Cy7-DBCO at the site where N 3 -Cy5-WGA was injected induced 80-90% quenching of the Cy5-related signal after 10-20 minutes, while the Cy7-related signal remained stable over time. In vivo, Cy7-DBCO effectively quenched the non-specific background signal up to 73% within 5 minutes, resulting in a 50% increase in the signal-to-background ratio between the nerve and injection site. Conclusion: The presented pretargeted fluorescence-quenching technology allowed fast and effective reduction of the background signal at the injection site, while preserving in vivo nerve visualization. While this proof-of-principle study was focused on imaging of nerves using a fluorescent WGA-lectin, the same concept could in the future also apply t...

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Fluorescent Lectins for Local in Vivo Visualization of Peripheral Nerves

Cited by 16 publications

References 44 publications

Targeted Optical Imaging Agents in Cancer: Focus on Clinical Applications

Targeted Optical Imaging Agents in Cancer: Focus on Clinical Applications

Emerging Intraoperative Imaging Modalities to Improve Surgical Precision

Fluorescence background quenching as a means to increase Signal to Background ratio - a proof of concept during Nerve Imaging

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