Validation of a Three-Dimensional Head and Neck Spheroid Model to Evaluate Cameras for NIR Fluorescence-Guided Cancer Surgery

Near-infrared (NIR) fluorescence-guided surgery is an innovative technique for the real-time visualization of resection margins. The aim of this study was to develop a head and neck multicellular tumor spheroid model and to explore the possibilities offered by it for the evaluation of cameras for NIR fluorescence-guided surgery protocols. FaDu spheroids were incubated with indocyanine green (ICG) and then included in a tissue-like phantom. To assess the capability of Fluobeam® NIR camera to detect ICG in tissues, FaDu spheroids exposed to ICG were embedded in 2, 5 or 8 mm of tissue-like phantom. The fluorescence signal was significantly higher between 2, 5 and 8 mm of depth for spheroids treated with more than 5 µg/mL ICG (p < 0.05). The fluorescence intensity positively correlated with the size of spheroids (p < 0.01), while the correlation with depth in the tissue-like phantom was strongly negative (p < 0.001). This multicellular spheroid model embedded in a tissue-like phantom seems to be a simple and reproducible in vitro tumor model, allowing a comparison of NIR cameras. The ideal configuration seems to be 450 μm FaDu spheroids incubated for 24 hours with 0.05 mg/ml of ICG, ensuring the best stability, toxicity, incorporation and signal intensity.

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Near-infrared (NIR) fluorescence imaging of head and neck squamous cell carcinoma for fluorescence-guided surgery (Conference Presentation)

Molecular-Guided Surgery: Molecules, Devices, and Applications II ◽

10.1117/12.2214002 ◽

2016 ◽

Author(s):

Lindsay Moore ◽

Jason M. Warram ◽

Esther de Boer ◽

William R. Carroll ◽

Anthony Morlandt ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Fluorescence Imaging ◽

Squamous Cell ◽

Near Infrared ◽

Neck Squamous Cell Carcinoma ◽

Guided Surgery ◽

Nir Fluorescence ◽

Fluorescence Guided Surgery

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Anti-GD2-IRDye800CW as a targeted probe for fluorescence-guided surgery in neuroblastoma

Scientific Reports ◽

10.1038/s41598-020-74464-4 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Lianne M. Wellens ◽

Marion M. Deken ◽

Cornelis F. M. Sier ◽

Hannah R. Johnson ◽

Fàtima de la Jara Ortiz ◽

...

Keyword(s):

Near Infrared ◽

Time Window ◽

Specific Binding ◽

Neoadjuvant Treatment ◽

Xenograft Model ◽

Fluorescence Signal ◽

Human Neuroblastoma ◽

Guided Surgery ◽

Fluorescence Guided Surgery ◽

Wide Range

Abstract Neuroblastoma resection represents a major challenge in pediatric surgery, because of the high risk of complications. Fluorescence-guided surgery (FGS) could lower this risk by facilitating discrimination of tumor from normal tissue and is gaining momentum in adult oncology. Here, we provide the first molecular-targeted fluorescent agent for FGS in pediatric oncology, by developing and preclinically evaluating a GD2-specific tracer consisting of the immunotherapeutic antibody dinutuximab-beta, recently approved for neuroblastoma treatment, conjugated to near-infrared (NIR) fluorescent dye IRDye800CW. We demonstrated specific binding of anti-GD2-IRDye800CW to human neuroblastoma cells in vitro and in vivo using xenograft mouse models. Furthermore, we defined an optimal dose of 1 nmol, an imaging time window of 4 days after administration and show that neoadjuvant treatment with anti-GD2 immunotherapy does not interfere with fluorescence imaging. Importantly, as we observed universal, yet heterogeneous expression of GD2 on neuroblastoma tissue of a wide range of patients, we implemented a xenograft model of patient-derived neuroblastoma organoids with differential GD2 expression and show that even low GD2 expressing tumors still provide an adequate real-time fluorescence signal. Hence, the imaging advancement presented in this study offers an opportunity for improving surgery and potentially survival of a broad group of children with neuroblastoma.

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One-pot synthesis of water-soluble near-infrared fluorescence RNase A capped CuInS2 quantum dots for in vivo imaging

RSC Advances ◽

10.1039/c7ra08418h ◽

2017 ◽

Vol 7 (80) ◽

pp. 50949-50954 ◽

Cited By ~ 5

Author(s):

Yue Xi ◽

Jianjun Yang ◽

Yunshen Ge ◽

Shenli Zhao ◽

Jianguang Wang ◽

...

Keyword(s):

Quantum Dots ◽

Near Infrared ◽

Rnase A ◽

Water Soluble ◽

One Pot ◽

Guided Surgery ◽

Nir Fluorescence ◽

Fluorescence Guided Surgery ◽

Cuins2 Quantum Dots

Near-infrared (NIR) quantum dots (QDs) have been treated as a promising candidate of imaging agents for NIR fluorescence-guided surgery. Here, the RNase A-CuInS2 QDs is good candidate, which performers well in gastrointestinal system imaging.

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uPAR-targeted optical near-infrared (NIR) fluorescence imaging and PET for image-guided surgery in head and neck cancer: proof-of-concept in orthotopic xenograft model

Oncotarget ◽

10.18632/oncotarget.14282 ◽

2016 ◽

Vol 8 (9) ◽

pp. 15407-15419 ◽

Cited By ~ 24

Author(s):

Anders Christensen ◽

Karina Juhl ◽

Morten Persson ◽

Birgitte Wittenborg Charabi ◽

Jann Mortensen ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Near Infrared ◽

Xenograft Model ◽

Image Guided Surgery ◽

Proof Of Concept ◽

Guided Surgery ◽

Image Guided ◽

Orthotopic Xenograft Model ◽

Nir Fluorescence

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Comparison of HER2-Targeted Antibodies for Fluorescence-Guided Surgery in Breast Cancer

Molecular Imaging ◽

10.1155/2021/5540569 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Solmaz AghaAmiri ◽

Jo Simien ◽

Alastair M. Thompson ◽

Julie Voss ◽

Sukhen C. Ghosh ◽

...

Keyword(s):

Breast Cancer ◽

Near Infrared ◽

Residual Disease ◽

Ex Vivo ◽

Guided Surgery ◽

Nirf Imaging ◽

Fluorescence Guided Surgery ◽

Imaging Results

Background. Although therapeutic advances have led to enhanced survival in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, detection of residual disease remains challenging. Here, we examine two approved anti-HER2 monoclonal antibodies (mAbs), trastuzumab and pertuzumab, as potential candidates for the development of immunoconjugates for fluorescence-guided surgery (FGS). Methods. mAbs were conjugated to the near-infrared fluorescent (NIRF) dye, IRDye800, and for quantitative in vitro assessment, to the radiometal chelator, desferrioxamine, to enable dual labeling with 89Zr. In vitro binding was evaluated in HER2-overexpressing (BT474, SKBR3) and HER2-negative (MCF7) cell lines. BT474 and MCF7 xenografts were used for in vivo and ex vivo fluorescence imaging. Results. In vitro findings demonstrated HER2-mediated binding for both fluorescent immunoconjugates and were in agreement with radioligand assays using dual-labeled immunoconjugates. In vivo and ex vivo studies showed preferential accumulation of the fluorescently-labeled mAbs in tumors and similar tumor-to-background ratios. In vivo HER2 specificity was confirmed by immunohistochemical staining of resected tumors and normal tissues. Conclusions. We showed for the first time that fluorescent trastuzumab and pertuzumab immunoconjugates have similar NIRF imaging performance and demonstrated the possibility of performing HER2-targeted FGS with agents that possess distinct epitope specificity.

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Intraoperative Near-Infrared Fluorescence Guided Surgery Using Indocyanine Green (ICG) for the Resection of Sarcomas May Reduce the Positive Margin Rate: An Extended Case Series

Cancers ◽

10.3390/cancers13246284 ◽

2021 ◽

Vol 13 (24) ◽

pp. 6284

Author(s):

Marcus J. Brookes ◽

Corey D. Chan ◽

Fabio Nicoli ◽

Timothy P. Crowley ◽

Kanishka M. Ghosh ◽

...

Keyword(s):

Indocyanine Green ◽

Near Infrared ◽

Positive Margin ◽

Randomised Control Trial ◽

High Grade ◽

Conventional Surgery ◽

Guided Surgery ◽

Positive Margin Rate ◽

Nir Fluorescence ◽

Fluorescence Guided Surgery

Background: Sarcomas are rare, aggressive cancers which can occur in any region of the body. Surgery is usually the cornerstone of curative treatment, with negative surgical margins associated with decreased local recurrence and improved overall survival. Indocyanine green (ICG) is a fluorescent dye which accumulates in sarcoma tissue and can be imaged intraoperatively using handheld near-infrared (NIR) cameras, theoretically helping guide the surgeon’s resection margins. Methods: Patients operated on between 20 February 2019 and 20 October 2021 for intermediate to high grade sarcomas at our centres received either conventional surgery, or were administered ICG pre-operatively followed by intra-operative NIR fluorescence guidance during the procedure. Differences between the unexpected positive margin rates were compared. Results: 115 suitable patients were identified, of which 39 received ICG + NIR fluorescence guided surgery, and 76 received conventional surgery. Of the patients given ICG, 37/39 tumours fluoresced, and surgeons felt the procedure was guided by the intra-operative images in 11 cases. Patients receiving ICG had a lower unexpected positive margin rate (5.1% vs. 25.0%, p = 0.01). Conclusions: The use of NIR fluorescence cameras in combination with ICG may reduce the unexpected positive margin rate for high grade sarcomas. A prospective, multi-centre randomised control trial is now needed to validate these results.

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Synthesis and in vitro preliminary evaluation of prostate-specific membrane antigen targeted upconversion nanoparticles as a first step towards radio/fluorescence-guided surgery of prostate cancer

Journal of Materials Chemistry B ◽

10.1039/d1tb00777g ◽

2021 ◽

Author(s):

Axel Cordonnier ◽

Damien Boyer ◽

Sophie Besse ◽

Rodolphe Valleix ◽

Rachid Mahiou ◽

...

Keyword(s):

Near Infrared ◽

Biological Tissues ◽

Upconversion Nanoparticles ◽

Preliminary Evaluation ◽

Prostate Specific Membrane Antigen ◽

Optical Window ◽

Guided Surgery ◽

Fluorescence Guided Surgery ◽

Specific Membrane

Over the last decade, upconversion nanoparticles (UCNP) have been widely investigated in nanomedicine due to their high potential as imaging agents in the near-infrared (NIR) optical window of biological tissues....

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Unexpected Binding of Tozuleristide “Tumor Paint” to Cerebral Vascular Malformations: A Potentially Novel Application of Fluorescence-Guided Surgery

Neurosurgery ◽

10.1093/neuros/nyab106 ◽

2021 ◽

Author(s):

Andrew J Kobets ◽

David Nauen ◽

Amy Lee ◽

Alan R Cohen

Keyword(s):

Near Infrared ◽

Vascular Malformations ◽

Cns Tumors ◽

Matrix Metalloproteinase 2 ◽

Cerebrovascular Lesions ◽

Cavernous Malformations ◽

Guided Surgery ◽

Fluorescence Guided Surgery ◽

Cerebral Vascular Malformations ◽

Cerebral Vascular

Abstract BACKGROUND Fluorescence-guided surgery (FGS) is under investigation as a means to improve the extent of resection for primary central nervous system (CNS) tumors. Tozuleristide, known also as “Tumor Paint,” is an investigational tumor-targeting agent covalently conjugated to a derivative of the fluorescent dye indocyanine green. OBJECTIVE To report the finding of avid intraoperative fluorescence of tozuleristide on cerebral vascular malformations. METHODS Our institution is participating in a phase 2/3 study of intraoperative near-infrared fluorescence detection of pediatric primary CNS tumors in patients receiving intravenous tozuleristide and imaged with the Canvas system. Our site enrolled 2 patients with intracranial lesions, suspected preoperatively of possibly being gliomas that proved to be cavernous vascular malformations after resection. RESULTS Each lesion had a dark blue mulberry appearance and each fluoresced avidly with tozuleristide. Each was completely resected, and the patients recovered without deficit. Pathological assessment showed cavernous angioma for both cases. Tozuleristide fluorescence is postulated to result from binding to matrix metalloproteinase-2 and annexin A2, and literature review demonstrates expression of both these ligands on multiple cerebrovascular lesions, including cavernous malformations. CONCLUSION This finding deserves further investigation to determine if tozuleristide “Tumor Paint” may have a wider role in the identification of non-neoplastic intracranial pathologies.

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