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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Quan Zhou ◽  
Johana C. M. Vega Leonel ◽  
Michelle Rai Santoso ◽  
Christy Wilson ◽  
Nynke S. van den Berg ◽  
...  

AbstractThe 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.

2020 ◽  
Author(s):  
Quan Zhou ◽  
Johana Vega Leonel ◽  
Michelle Santoso ◽  
Christy Wilson ◽  
Nynke van den Berg ◽  
...  

Abstract 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.


2022 ◽  
Vol 6 (1) ◽  
pp. V9

A contrast-enhancing lesion in the left temporal lobe of a 72-year-old woman was biopsied and diagnosed as glioblastoma. Near-infrared (NIR)–labeled epidermal growth factor receptor (EGFR) antibody, panitumumab-IRDye800, was infused 52 hours before craniotomy without pretreatment. Tumor fluorescence was detected through intact dura, and the visual contrast between disease and peritumoral healthy brain was enhanced after tumor exposure. Residual cancerous tissue was identified with strong fluorescence in resection cavity after en bloc tumor removal. Minimal fluorescence remained in the final wound bed, likely from nonenhancing tumor. Fluorescence was heterogeneously distributed at the infiltrative margin in resected tumor pieces imaged ex vivo. Postoperative MRI confirmed gross-total resection. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21201


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lydian A. Huisman ◽  
Pieter J. Steinkamp ◽  
Jan-Luuk Hillebrands ◽  
Clark J. Zeebregts ◽  
Matthijs D. Linssen ◽  
...  

AbstractVascular endothelial growth factor-A (VEGF-A) is assumed to play a crucial role in the development and rupture of vulnerable plaques in the atherosclerotic process. We used a VEGF-A targeted fluorescent antibody (bevacizumab-IRDye800CW [bevacizumab-800CW]) to image and visualize the distribution of VEGF-A in (non-)culprit carotid plaques ex vivo. Freshly endarterectomized human plaques (n = 15) were incubated in bevacizumab-800CW ex vivo. Subsequent NIRF imaging showed a more intense fluorescent signal in the culprit plaques (n = 11) than in the non-culprit plaques (n = 3). A plaque received from an asymptomatic patient showed pathologic features similar to the culprit plaques. Cross-correlation with VEGF-A immunohistochemistry showed co-localization of VEGF-A over-expression in 91% of the fluorescent culprit plaques, while no VEGF-A expression was found in the non-culprit plaques (p < 0.0001). VEGF-A expression was co-localized with CD34, a marker for angiogenesis (p < 0.001). Ex vivo near-infrared fluorescence (NIRF) imaging by incubation with bevacizumab-800CW shows promise for visualizing VEGF-A overexpression in culprit atherosclerotic plaques in vivo.


Sarcoma ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Séverine Tabone-Eglinger ◽  
Radislav Bahleda ◽  
Jean-François Côté ◽  
Philippe Terrier ◽  
Dominique Vidaud ◽  
...  

Malignant peripheral nerve sheath tumours (MPNSTs) are highly malignant and resistant. Transformation might implicate up regulation of epidermal growth factor receptor (EGFR). Fifty-two MPNST samples were studied for EGFR, Ki-67, p53, and survivin expression by immunohistochemistry and forEGFRamplification by in situ hybridization. Results were correlated with clinical data.EGFRRNA was also quantified by RT-PCR in 20 other MPNSTs and 14 dermal neurofibromas. Half of the patients had a neurofibromatosis type 1 (NF1). EGFR expression, detected in 86% of MPNSTs, was more frequent in NF1 specimens and closely associated with high-grade and p53-positive areas. MPNSTs expressed moreEGFRtranscripts than neurofibromas. No amplification ofEGFRlocus was observed. NF1 status was the only prognostic factor in multivariate analysis, with median survivals of 18 and 43 months for patients with or without NF1. Finally, EGFR might become a new target for MPNSTs treatment, especially in NF1-associated MPNSTs.


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