A fluorescent photoimmunoconjugate for imaging of cholesteatoma

Samuel Early; M Ahsan Saad; Srivalleesha Mallidi; Amer Mansour; Richard Seist; Tayyaba Hasan; Konstantina M Stankovic

doi:10.1038/s41598-022-22072-9

A fluorescent photoimmunoconjugate for imaging of cholesteatoma

Sci Rep. 2022 Nov 19;12(1):19905. doi: 10.1038/s41598-022-22072-9.

Authors

Samuel Early^{1

2

3}, M Ahsan Saad⁴, Srivalleesha Mallidi^{4

5}, Amer Mansour¹, Richard Seist^{1

2

6}, Tayyaba Hasan⁴, Konstantina M Stankovic^{7

8

9}

Affiliations

¹ Department of Otolaryngology - Head and Neck Surgery and Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, USA.
² Department of Otolaryngology - Head and Neck Surgery, Harvard Medical School, Boston, MA, USA.
³ Department of Otolaryngology - Head and Neck Surgery, University of California San Diego Medical Center, San Diego, CA, USA.
⁴ Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.
⁵ Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
⁶ Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Department of Otolaryngology - Head and Neck Surgery and Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, USA. kstankovic@stanford.edu.
⁸ Department of Otolaryngology - Head and Neck Surgery, Harvard Medical School, Boston, MA, USA. kstankovic@stanford.edu.
⁹ Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA. kstankovic@stanford.edu.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Cholesteatoma, Middle Ear* / diagnostic imaging
Cholesteatoma, Middle Ear* / surgery
Coloring Agents
Diagnostic Imaging
Ear, Middle
Hearing Tests
Humans
Mice

Substances

Coloring Agents

Grants and funding

R01 DC015824/DC/NIDCD NIH HHS/United States