Optical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer

Nishio, Naoki; Berg, Nynke S. van den; Keulen, Stan van; Martin, Brock A.; Fakurnejad, Shayan; Teraphongphom, Nutte; Chirita, Stefania U.; Oberhelman, Nicholas J.; Lu, Guolan; Horton, Crista; Kaplan, Michael; Divi, Vasu; Colevas, A. Dimitrios

doi:10.1038/s41467-019-13076-7

Cited by 79 publications

(66 citation statements)

References 35 publications

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“…They were incubated overnight at 4 °C with either a commercial unlabeled EGFR antibody (1:2.5, RM-2111-RQ, rabbit-anti-human, Thermo Scientific) followed by secondary antibody (Alexa Fluor 594, Invitrogen) in blocking buffer for one hour at room temperature, or a NIR-labeled human EGFR antibody, panitumumab-IRDye800 (5 nM, Leidos www.nature.com/scientificreports/ Biomedical Research Center, Frederick, MD). Slides were counterstaining with 4′, 6-diamidino-2-phenylindole (DAPI, 300 nM, Invitrogen), and imaged using a Zeiss LSM710 confocal fluorescence microscope or a custombuilt fluorescence microscope (Leica) 45 . Mean fluorescence intensities (MFIs) from 10 cells per image in five images were normalized to that of the positive control (SCC-1) using ImageJ (v1.52p).…”

Section: Methodsmentioning

confidence: 99%

Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma

Zhou

Leonel

Santoso

et al. 2021

Sci Rep

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The prognosis for high-grade glioma (HGG) remains dismal and the extent of resection correlates with overall survival and progression free disease. Epidermal growth factor receptor (EGFR) is a biomarker heterogeneously expressed in HGG. We assessed the feasibility of detecting HGG using near-infrared fluorescent antibody targeting EGFR. Mice bearing orthotopic HGG xenografts with modest EGFR expression were imaged in vivo after systemic panitumumab-IRDye800 injection to assess its tumor-specific uptake macroscopically over 14 days, and microscopically ex vivo. EGFR immunohistochemical staining of 59 tumor specimens from 35 HGG patients was scored by pathologists and expression levels were compared to that of mouse xenografts. Intratumoral distribution of panitumumab-IRDye800 correlated with near-infrared fluorescence and EGFR expression. Fluorescence distinguished tumor cells with 90% specificity and 82.5% sensitivity. Target-to-background ratios peaked at 14 h post panitumumab-IRDye800 infusion, reaching 19.5 in vivo and 7.6 ex vivo, respectively. Equivalent or higher EGFR protein expression compared to the mouse xenografts was present in 77.1% HGG patients. Age, combined with IDH-wildtype cerebral tumor, was predictive of greater EGFR protein expression in human tumors. Tumor specific uptake of panitumumab-IRDye800 provided remarkable contrast and a flexible imaging window for fluorescence-guided identification of HGGs despite modest EGFR expression.

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Section: Methodsmentioning

confidence: 99%

Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma

Zhou

Leonel

Santoso

et al. 2021

Sci Rep

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“…26 We and others have reported the feasibility and potential clinical benefits of FGS using antibody dye-based imaging for patients with solid tumors. 10,11,[13][14][15][16][17][18][27][28][29][30][31] Combining FGS with the advantages of a minimally invasive, endoscopic approach may hold the potential to reduce morbidity while ensuring adequate oncologic outcomes. However, this has yet to be further investigated and validated in large prospective trials.…”

Section: Discussionmentioning

confidence: 99%

“…Utilizing NIR fluorescence imaging using ICG with laparoscopic and robot‐assisted surgery have improved oncologic outcomes reported in procedures such as hepatectomy, 23 nephrectomy, 24 hysterectomy, 25 and gastrectomy 26 . We and others have reported the feasibility and potential clinical benefits of FGS using antibody dye–based imaging for patients with solid tumors 10–11,13–18,27–31 . Combining FGS with the advantages of a minimally invasive, endoscopic approach may hold the potential to reduce morbidity while ensuring adequate oncologic outcomes.…”

Section: Discussionmentioning

confidence: 99%

Endoscopic Fluorescence‐Guided Surgery for Sinonasal Cancer Using an Antibody‐Dye Conjugate

et al. 2019

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Endoscopic resection of sinonasal squamous cell carcinoma has become the standard of care, but challenges remain in obtaining clear resection margins. The current study evaluated the feasibility of endoscopic fluorescence-guided surgery (FGS) to improve surgical resection in a human sinus surgical model. Methods: A fluorescence endoscope optimized for near-infrared (NIR) fluorescence detection was evaluated in a phantom study. Various endoscope diameters (4 and 10 mm) and viewing angles (0, 30, and 45 degrees) were evaluated to determine the sensitivity of the system for IRDye800CW detection at various working distances (1-5 cm). Endoscopic FGS was then validated in a three-dimensional human sinus surgical model to which squamous cell tumors derived from mice were inserted. Mice had received intravenous panitumumab-IRDye800CW and upon fluorescence-guided tumor resection, mean fluorescence intensity (MFI) and tumor-to-background ratio (TBR) were calculated in in situ and ex vivo settings. Results: A significantly higher fluorescence intensity was found when using the 10-mm diameter endoscope compared to the 4mm diameter endoscope (P < .001). No significant difference in MFI was found among the viewing angles of the 4-mm diameter endoscope. Using the human sinus model, the highest MFI and TBR were obtained at a 1-cm working distance compared to longer working distances. Conclusion: We demonstrate that clinically acceptable TBRs were obtained with several working distances to discriminate tumor tissue from adjacent normal tissue in a human sinus model, and that endoscopic FGS may have great potential in identifying residual tumor tissue regions during surgery.

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“…Slides were counterstaining with 4', 6-diamidino-2-phenylindole (DAPI, 300nM, Invitrogen), and imaged using a Zeiss LSM710 confocal fluorescence microscope or a custom-built fluorescence microscope (Leica). 31 Mean fluorescence intensities (MFIs) from 10 cells per image in five images were normalized to that of the positive control (SCC-1) using Image J (v1.52p). following 3 kDa fluorescein-dextran injection (10mg/ml, i.v., ThermoFisher).…”

Section: Immunofluorescence Analysismentioning

confidence: 99%

“…Anesthesia was induced with 5% isoflurane and maintained with 2% isoflurane in room air and labeled tomato lectin (10 µg/ml, Vector Laboratories) for 30 minutes and counterstained with DAPI (300nM, Invitrogen) before they were imaged with a custom-built fluorescence microscope (Leica). 31 MFIs were measured from 10 randomly selected cells in three views.…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

Antibody-Dye Conjugate Detects Epidermal Growth Factor Receptor Expression in High-Graded Gliomas: A Feasibility Study for Fluorescence-Guided Resection

Zhou¹,

Leonel²,

Santoso³

et al. 2020

Preprint

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Background: The prognosis for high-grade glioma (HGG) remains dismal and extent of resection correlates with overall survival and progression free disease. Epidermal growth factor receptor (EGFR) is a biomarker heterogeneously expressed in HGG. We assessed the feasibility of detecting HGG using near-infrared fluorescent antibody targeting EGFR. Methods: Mice bearing orthotopic HGG xenografts with modest EGFR expression were imaged in vivo after systemic panitumumab-IRDye800 injection to assess its tumor-specific uptake macroscopically over 14 days, and microscopically ex vivo. EGFR immunohistochemical staining of 59 tumor specimens from 35 HGG patients during was scored by pathologists and expression levels were compared to that of mouse xenografts. Results: Intratumoral distribution of pan800 correlated with near-infrared fluorescence and EGFR expression. Fluorescence distinguished tumor cells with 90% specificity and 82.5% sensitivity. Target-to-background ratios peaked at 14 hours post panitumumab-IRDye800 infusion, reaching 19.5 in vivo and 7.6 ex vivo, respectively. Equivalent or higher EGFR protein expression compared to the mouse xenografts was present in 77.1% HGG patients. Age, combined with IDH-wildtype cerebral tumor, was predictive of greater EGFR protein expression in human tumors. Conclusion: Tumor specific uptake of pan800 provided remarkable contrast and a flexible imaging window for fluorescence-guided identification of HGGs despite modest EGFR expression.

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Optical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer

Cited by 79 publications

References 35 publications

Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma

Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma

Endoscopic Fluorescence‐Guided Surgery for Sinonasal Cancer Using an Antibody‐Dye Conjugate

Antibody-Dye Conjugate Detects Epidermal Growth Factor Receptor Expression in High-Graded Gliomas: A Feasibility Study for Fluorescence-Guided Resection

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