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Paired-Agent Imaging for Fluorescence-Guided Surgery in Head and Neck Cancer

Abstract

Head and neck cancer is the sixth common type of cancer worldwide. Surgical resection is a common first-line treatment, with the goal of maximizing tumor removal while preserving the functionality of vital structures. Completeness of surgical resection is a critical determinant for the survival of patients. Positive tumor margins in oral cavity tumors increases tumor-related death at 5-years by 90% compared to those with truly negative margins, but the use of wide margins to remove residual tumor in the head and neck region can lead to severe morbidity. Fluorescence guided surgery (FGS), aimed to provide surgeons with real-time molecular overexpression information to differentiate tumor compared to normal tissue, has taken off over the last several decades with the development in novel probes and imaging systems. However, non-specific uptake and retention of molecular targeted agents, and heterogeneous tissue optical properties diminish the ability to differentiate between tumor and normal tissues using molecular targeted fluorescent agents. The paired agent imaging (PAI) method has the potential to overcome high background induced by nonspecific uptake in FGS through kinetic compensation with untargeted fluorescent agent, providing standardized, highly accurate visualization of tumor with true molecular binding events that cannot be achieved by conventional single agent imaging (SAI).

This thesis proposal is focused on applying PAI in FGS to improve the diagnostic ability and margin assessment of head and neck cancer, and ultimately improve the surgical therapeutic index. The targeted agent, a near-infrared fluorescent anti-epidermal growth factor receptor (EGFR) Affibody molecule, ABY-029, combined with a suitable untargeted agent are co-administered and co-imaged in PAI. The pre-clinical study of PAI is presented and performance is compared with conventional single agent imaging in orthotopic xenograft mouse models of human and neck cancer. To optimize PAI in FGS, three clinically relevant untargeted agents were examined to determine the best candidate for clinical translation of ABY-029 PAI. Furthermore, the application of PAI in frozen section analysis for intraoperative margin assessment and accuracy of single time point ratio-metric mathematic model will be examined. These PAI feasibility studies provide a logical and clear step for translation of PAI into clinical practice.

Thesis Committee

• Kimberley S. Samkoe (chair)
• P. Jack Hoops
• Jonathan T. Elliott
• Kenneth M. Tichauer (Illinois Institute of Technology)

Contact

For more information, contact Theresa Fuller at theresa.d.fuller@dartmouth.edu.