Author ORCID Identifier

https://orcid.org/0009-0005-0690-4224

Date of Award

Spring 4-30-2026

Document Type

Thesis (Ph.D.)

Department or Program

Engineering Sciences

First Advisor

Kimberley Samkoe

Abstract

Surgical resection remains to be the cornerstone of treatment for most solid tumors, where the primary objective is to remove all visible and microscopic disease. However, the extent of tumor resection is inherently limited by the surgeon’s ability to distinguish tumor from normal tissue, intraoperatively. As a result, positive surgical margins (PSM), where residual tumor remains after surgery, are a common occurrence and are associated with increased recurrence, need for adjuvant therapies, dismal patient outcomes, and high healthcare costs.

Fluorescence guided surgery (FGS) has emerged as a promising technique to enhance intraoperative visualization of tumors and may help reduce the incidence of PSM. Current FGS methods typically rely on a single fluorescent agent, which may target tumor-specific biomarkers or accumulate through nonspecific mechanisms. Although these agents can improve gross tumor visualization, they suffer from limitations such as high nonspecific signal in normal tissue and a lack of quantitative information, often resulting in ambiguous interpretation.

This thesis presents and evaluates a novel quantitative fluorescence imaging approach, Paired Agent Imaging (PAI), developed to overcome the limitations of single agent FGS. PAI utilizes two co-administered agents: a targeted agent that binds to tumor-specific receptors and an untargeted control agent that is non-binding and provides a reference for nonspecific uptake. By correcting for nonspecific signal, PAI not only enhances tumor contrast but also enables in vivo quantification of receptor availability.

The overarching aim of this thesis is to investigate the utility of PAI to improve surgical decision-making in head and neck squamous cell carcinoma (HNSCC), glioma, and epithelial ovarian cancer (EOC). For HNSCC, we established key clinical parameters for translation, demonstrating that PAI is independent of imaging agent concentration and provides stable signal from 2-24 hours post-injection. In glioma, we compared PAI with single-agent FGS approaches and validated both against tissue pathology. For EOC, we developed a PAI endoscope to preoperative stage tumor burden and assess surgical eligibility. Together, these studies demonstrate that PAI holds significant potential as a quantitative intraoperative imaging tool to improve tumor visualization, reduce positive margins, and ultimately enhance patient outcomes across a range of solid tumors.

Download

Share

COinS