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Targeted Photodynamic Therapy of Human Head and Neck Squamous Cell Carcinoma with Anti‐epidermal Growth Factor Receptor Antibody Cetuximab and Photosensitizer IR700DX in the Mouse Skin‐fold Window Chamber Model
Author(s) -
Peng Wei,
Bruijn Henriette S.,
Hagen Timo L. M.,
Dam Go M.,
Roodenburg Jan L. N.,
Berg Kristian,
Witjes Max J. H.,
Robinson Dominic J.
Publication year - 2020
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.13267
Subject(s) - photodynamic therapy , cetuximab , immunohistochemistry , photosensitizer , epidermal growth factor receptor , pathology , cancer research , epidermal growth factor , antibody , biology , chemistry , receptor , medicine , monoclonal antibody , immunology , organic chemistry
Abstract Targeted photodynamic therapy (PDT) in head/neck cancer patients with a conjugate of the anti‐epidermal growth factor receptor (EGFR) antibody, Cetuximab and a phthalocyanine photosensitizer IR700DX is under way, but the exact mechanisms of action are still not fully understood. In this study, the EGFR‐overexpressing human head/neck OSC‐19‐luc2‐cGFP tumor with transfected GFP gene was used in a skin‐fold window chamber model in BALB/c nude mice. The uptake and localization of the conjugate in the tumor and its surrounding normal tissues were studied by an intravital confocal laser scanning microscopy with image analyses. The tumor was also irradiated with 690 nm laser light 24 h after conjugate administration. The vascular and tumor responses were examined by morphological evaluation and immunohistochemistry (IHC). The amount of conjugate in the tumor peaked at 24–48 h after injection. Image analyses of colocalization correlation parameters demonstrated a high fraction of the conjugate IR700DX colocalized in the GFP‐expressing tumor cells. PDT‐treated tumors showed extensive necrotic/apoptotic destruction with little vascular damage, while IHC showed no HIF‐1α expression and decreased EGFR and Ki67 expression with activated caspase‐3 overexpression, indicating a direct killing of tumor cells through both necrotic and apoptotic cell death.