In Vivo Fluorescence Immunohistochemistry: Localization of Fluorescently Labeled Cetuximab in Squamous Cell Carcinomas

Esther de Boer; Jason M. Warram; Matthew D. Tucker; Yolanda E. Hartman; Lindsay S. Moore; Johannes S. de Jong; Thomas K. Chung; Melissa L. Korb; Kurt R. Zinn; Gooitzen M. van Dam; Eben L. Rosenthal; Margaret S. Brandwein-Gensler

doi:10.1038/srep10169

In Vivo Fluorescence Immunohistochemistry: Localization of Fluorescently Labeled Cetuximab in Squamous Cell Carcinomas

Esther de Boer, Jason M. Warram, Matthew D. Tucker, Yolanda E. Hartman, Lindsay S. Moore, Johannes S. de Jong, Thomas K. Chung, Melissa L. Korb, Kurt R. Zinn, Gooitzen M. van Dam, Eben L. Rosenthal^*, Margaret S. Brandwein-Gensler

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Anti-EGFR (epidermal growth factor receptor) antibody based treatment strategies have been successfully implemented in head and neck squamous cell carcinoma (HNSCC). Unfortunately, predicting an accurate and reliable therapeutic response remains a challenge on a per-patient basis. Although significant efforts have been invested in understanding EGFR-mediated changes in cell signaling related to treatment efficacy, the delivery and histological localization in (peri-) tumoral compartments of antibody-based therapeutics in human tumors is poorly understood nor ever made visible. In this first in-human study of a systemically administered near-infrared (NIR) fluorescently labeled therapeutic antibody, cetuximab-IRDye800CW (2.5 mg/m(2), 25 mg/m(2), and 62.5 mg/m(2)), we show that by optical molecular imaging (i.e. denominated as In vivo Fluorescence Immunohistochemistry) we were able to evaluate localization of fluorescently labeled cetuximab. Clearly, optical molecular imaging with fluorescently labeled antibodies correlating morphological (peri-) tumoral characteristics to levels of antibody delivery, may improve treatment paradigms based on understanding true tumoral antibody delivery.

Original language	English
Article number	10169
Number of pages	11
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep10169
Publication status	Published - 29-Jun-2015

Keywords

GROWTH-FACTOR RECEPTOR
NECK-CANCER
EGFR-INHIBITORS
HEAD
TARGET

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de Boer, E., Warram, J. M., Tucker, M. D., Hartman, Y. E., Moore, L. S., de Jong, J. S., Chung, T. K., Korb, M. L., Zinn, K. R., van Dam, G. M., Rosenthal, E. L., & Brandwein-Gensler, M. S. (2015). In Vivo Fluorescence Immunohistochemistry: Localization of Fluorescently Labeled Cetuximab in Squamous Cell Carcinomas. Scientific Reports, 5, Article 10169. https://doi.org/10.1038/srep10169

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title = "In Vivo Fluorescence Immunohistochemistry: Localization of Fluorescently Labeled Cetuximab in Squamous Cell Carcinomas",

abstract = "Anti-EGFR (epidermal growth factor receptor) antibody based treatment strategies have been successfully implemented in head and neck squamous cell carcinoma (HNSCC). Unfortunately, predicting an accurate and reliable therapeutic response remains a challenge on a per-patient basis. Although significant efforts have been invested in understanding EGFR-mediated changes in cell signaling related to treatment efficacy, the delivery and histological localization in (peri-) tumoral compartments of antibody-based therapeutics in human tumors is poorly understood nor ever made visible. In this first in-human study of a systemically administered near-infrared (NIR) fluorescently labeled therapeutic antibody, cetuximab-IRDye800CW (2.5 mg/m(2), 25 mg/m(2), and 62.5 mg/m(2)), we show that by optical molecular imaging (i.e. denominated as In vivo Fluorescence Immunohistochemistry) we were able to evaluate localization of fluorescently labeled cetuximab. Clearly, optical molecular imaging with fluorescently labeled antibodies correlating morphological (peri-) tumoral characteristics to levels of antibody delivery, may improve treatment paradigms based on understanding true tumoral antibody delivery.",

keywords = "GROWTH-FACTOR RECEPTOR, NECK-CANCER, EGFR-INHIBITORS, HEAD, TARGET",

author = "{de Boer}, Esther and Warram, {Jason M.} and Tucker, {Matthew D.} and Hartman, {Yolanda E.} and Moore, {Lindsay S.} and {de Jong}, {Johannes S.} and Chung, {Thomas K.} and Korb, {Melissa L.} and Zinn, {Kurt R.} and {van Dam}, {Gooitzen M.} and Rosenthal, {Eben L.} and Brandwein-Gensler, {Margaret S.}",

year = "2015",

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doi = "10.1038/srep10169",

language = "English",

volume = "5",

journal = "Scientific Reports",

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T2 - Localization of Fluorescently Labeled Cetuximab in Squamous Cell Carcinomas

AU - de Boer, Esther

AU - Warram, Jason M.

AU - Tucker, Matthew D.

AU - Hartman, Yolanda E.

AU - Moore, Lindsay S.

AU - de Jong, Johannes S.

AU - Chung, Thomas K.

AU - Korb, Melissa L.

AU - Zinn, Kurt R.

AU - van Dam, Gooitzen M.

AU - Rosenthal, Eben L.

AU - Brandwein-Gensler, Margaret S.

PY - 2015/6/29

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N2 - Anti-EGFR (epidermal growth factor receptor) antibody based treatment strategies have been successfully implemented in head and neck squamous cell carcinoma (HNSCC). Unfortunately, predicting an accurate and reliable therapeutic response remains a challenge on a per-patient basis. Although significant efforts have been invested in understanding EGFR-mediated changes in cell signaling related to treatment efficacy, the delivery and histological localization in (peri-) tumoral compartments of antibody-based therapeutics in human tumors is poorly understood nor ever made visible. In this first in-human study of a systemically administered near-infrared (NIR) fluorescently labeled therapeutic antibody, cetuximab-IRDye800CW (2.5 mg/m(2), 25 mg/m(2), and 62.5 mg/m(2)), we show that by optical molecular imaging (i.e. denominated as In vivo Fluorescence Immunohistochemistry) we were able to evaluate localization of fluorescently labeled cetuximab. Clearly, optical molecular imaging with fluorescently labeled antibodies correlating morphological (peri-) tumoral characteristics to levels of antibody delivery, may improve treatment paradigms based on understanding true tumoral antibody delivery.

AB - Anti-EGFR (epidermal growth factor receptor) antibody based treatment strategies have been successfully implemented in head and neck squamous cell carcinoma (HNSCC). Unfortunately, predicting an accurate and reliable therapeutic response remains a challenge on a per-patient basis. Although significant efforts have been invested in understanding EGFR-mediated changes in cell signaling related to treatment efficacy, the delivery and histological localization in (peri-) tumoral compartments of antibody-based therapeutics in human tumors is poorly understood nor ever made visible. In this first in-human study of a systemically administered near-infrared (NIR) fluorescently labeled therapeutic antibody, cetuximab-IRDye800CW (2.5 mg/m(2), 25 mg/m(2), and 62.5 mg/m(2)), we show that by optical molecular imaging (i.e. denominated as In vivo Fluorescence Immunohistochemistry) we were able to evaluate localization of fluorescently labeled cetuximab. Clearly, optical molecular imaging with fluorescently labeled antibodies correlating morphological (peri-) tumoral characteristics to levels of antibody delivery, may improve treatment paradigms based on understanding true tumoral antibody delivery.

KW - GROWTH-FACTOR RECEPTOR

KW - NECK-CANCER

KW - EGFR-INHIBITORS

KW - HEAD

KW - TARGET

U2 - 10.1038/srep10169

DO - 10.1038/srep10169

M3 - Article

SN - 2045-2322

VL - 5

JO - Scientific Reports

JF - Scientific Reports

M1 - 10169

ER -

In Vivo Fluorescence Immunohistochemistry: Localization of Fluorescently Labeled Cetuximab in Squamous Cell Carcinomas

Abstract

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