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

Abstract 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 nea...

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Autores principales:	Quan Zhou, Johana C. M. Vega Leonel, Michelle Rai Santoso, Christy Wilson, Nynke S. van den Berg, Carmel T. Chan, Muna Aryal, Hannes Vogel, Romain Cayrol, Michael J. Mandella, Frank Schonig, Guolan Lu, Sanjiv S. Gambhir, Michael E. Moseley, Eben L. Rosenthal, Gerald A. Grant
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/221b0fd8becb4a9a9cf3556f71c46c2e
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spelling	oai:doaj.org-article:221b0fd8becb4a9a9cf3556f71c46c2e2021-12-02T11:37:18ZMolecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma10.1038/s41598-021-84831-42045-2322https://doaj.org/article/221b0fd8becb4a9a9cf3556f71c46c2e2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84831-4https://doaj.org/toc/2045-2322Abstract 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.Quan ZhouJohana C. M. Vega LeonelMichelle Rai SantosoChristy WilsonNynke S. van den BergCarmel T. ChanMuna AryalHannes VogelRomain CayrolMichael J. MandellaFrank SchonigGuolan LuSanjiv S. GambhirMichael E. MoseleyEben L. RosenthalGerald A. GrantNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Quan Zhou Johana C. M. Vega Leonel Michelle Rai Santoso Christy Wilson Nynke S. van den Berg Carmel T. Chan Muna Aryal Hannes Vogel Romain Cayrol Michael J. Mandella Frank Schonig Guolan Lu Sanjiv S. Gambhir Michael E. Moseley Eben L. Rosenthal Gerald A. Grant Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma
description	Abstract 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.
format	article
author	Quan Zhou Johana C. M. Vega Leonel Michelle Rai Santoso Christy Wilson Nynke S. van den Berg Carmel T. Chan Muna Aryal Hannes Vogel Romain Cayrol Michael J. Mandella Frank Schonig Guolan Lu Sanjiv S. Gambhir Michael E. Moseley Eben L. Rosenthal Gerald A. Grant
author_facet	Quan Zhou Johana C. M. Vega Leonel Michelle Rai Santoso Christy Wilson Nynke S. van den Berg Carmel T. Chan Muna Aryal Hannes Vogel Romain Cayrol Michael J. Mandella Frank Schonig Guolan Lu Sanjiv S. Gambhir Michael E. Moseley Eben L. Rosenthal Gerald A. Grant
author_sort	Quan Zhou
title	Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma
title_short	Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma
title_full	Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma
title_fullStr	Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma
title_full_unstemmed	Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma
title_sort	molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/221b0fd8becb4a9a9cf3556f71c46c2e
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Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma

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