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.
authors.affiliation: Division of Otolaryngology, University of Alabama at Birmingham, USA.|Department of Surgery, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: de Boer
authors.affiliation: Division of Otolaryngology, University of Alabama at Birmingham, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Warram
authors.affiliation: Division of Otolaryngology, University of Alabama at Birmingham, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Tucker
authors.affiliation: Division of Otolaryngology, University of Alabama at Birmingham, USA.
authors.forename: Yolanda E
authors.initials: YE
authors.lastname: Hartman
authors.affiliation: Division of Otolaryngology, University of Alabama at Birmingham, USA.
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Moore
authors.affiliation: Department of Pathology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
authors.forename: Johannes S
authors.initials: JS
authors.lastname: de Jong
authors.affiliation: Division of Otolaryngology, University of Alabama at Birmingham, USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Chung
authors.affiliation: Division of Otolaryngology, University of Alabama at Birmingham, USA.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Korb
authors.affiliation: Division of Advanced Medical Imaging, Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Zinn
authors.affiliation: Department of Surgery, Nuclear Medicine and Molecular Imaging and Intensive Care, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Gooitzen M
authors.initials: GM
authors.lastname: van Dam
authors.affiliation: Division of Otolaryngology, University of Alabama at Birmingham, USA.
authors.forename: Eben L
authors.initials: EL
authors.lastname: Rosenthal
authors.affiliation: Division of Anatomic Pathology, Department of Pathology, University of Alabama at Birmingham, USA.
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Brandwein-Gensler
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000378:metabolism; D015999:Multivariate Analysis
chemical_list: D005456:Fluorescent Dyes; C427728:IRDye800; D007211:Indoles; D066246:ErbB Receptors; D000068818:Cetuximab