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Abstract
Cholesteatoma is a potentially serious complication of chronic ear infections and requires surgical intervention for definitive management. Long-term complications include a frequent need for repeat surgical intervention for disease recurrence, and techniques to improve efficacy of single-stage surgery are an important area of continued research. This study investigates a novel application of the photosensitizer immune conjugate (PIC) cetuximab-benzoporphyrin derivative (Cet-BPD) for in vitro localization of human cholesteatoma tissue, coupled with an in vivo safety study for middle ear application of Cet-BPD in a murine model. In fresh human cholesteatoma tissues, Cet-BPD demonstrates selective localization to the hyperplastic squamous cell tissue associated with cholesteatoma, without localizing to other tissues such as middle ear mucosa. Applied to the murine middle ear, Cet-BPD does not demonstrate any deleterious effect on murine hearing when assessed by any of auditory brainstem response (ABR) thresholds, distortion product otoacoustic emission thresholds, or ABR wave I amplitudes. These findings demonstrate the technical promise and encouraging safety profile for the use of PICs for intraoperative localization and treatment of cholesteatoma.
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Details
1 Massachusetts Eye and Ear, Department of Otolaryngology – Head and Neck Surgery and Eaton-Peabody Laboratories, Boston, USA (GRID:grid.39479.30) (ISNI:0000 0000 8800 3003); Harvard Medical School, Department of Otolaryngology – Head and Neck Surgery, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); University of California San Diego Medical Center, Department of Otolaryngology – Head and Neck Surgery, San Diego, USA (GRID:grid.413086.8) (ISNI:0000 0004 0435 1668)
2 Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924)
3 Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Tufts University, Department of Biomedical Engineering, Medford, USA (GRID:grid.429997.8) (ISNI:0000 0004 1936 7531)
4 Massachusetts Eye and Ear, Department of Otolaryngology – Head and Neck Surgery and Eaton-Peabody Laboratories, Boston, USA (GRID:grid.39479.30) (ISNI:0000 0000 8800 3003)
5 Massachusetts Eye and Ear, Department of Otolaryngology – Head and Neck Surgery and Eaton-Peabody Laboratories, Boston, USA (GRID:grid.39479.30) (ISNI:0000 0000 8800 3003); Harvard Medical School, Department of Otolaryngology – Head and Neck Surgery, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Stanford University School of Medicine, Department of Otolaryngology – Head and Neck Surgery, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956)