ORCID ID
Graduation Date
Spring 5-7-2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Programs
Cancer Research
First Advisor
Aaron Mohs
Abstract
Pancreatic cancer, a termed lethal malignancy, is characterized by a dismal prognosis. Presently, the only potentially curative treatment option for pancreatic cancer is surgical resection, providing an increase in 5-year survival rates from 6% to 27% for patients undergoing resection. Yet up to 83% of patients that have undergone resection relapse due to the incomplete removal of the tumor. The possibility of an incomplete resection is in part due to challenges regarding a lack of intraoperative tumor identification. The imaging technique of fluorescence-guided surgery (FGS) provides a promising visual aid for surgeons during resection.
The functional application of FGS involves the specific binding of a fluorescent probe to allow for the accumulation of fluorescent signal in the solid tumor as opposed to normal tissue, thus, allowing surgeons to visualize the tumor intraoperatively. FGS is currently being used in clinical trials with several different fluorescent probes and target molecules. Antibodies and near-infrared fluorophores (NIRF) have proven efficacious in combination for the use of a fluorescent probe. Particularly, high sensitivity and specificity at low doses were observed with antibodies conjugated to a fluorophore known as IRDye800. Although these fluorescent probes displayed efficacy, they also illustrated the challenges of generating highly selective binding in tumorous tissue and avoiding nontargeted signal.
To address this challenge, we are investigating a protein known as mucin16 (MUC16) that is generally overexpressed in 60-80% of pancreatic ductal adenocarcinoma (PDAC), whilst not being expressed in inflamed or normal pancreatic tissue. A novel, humanized, monoclonal MUC16 antibody, named huAR9.6 has been generated for these studies. Initial experiments conjugating huAR9.6 to the NIR fluorophore, IRDye800, have proven preclinical efficacy both in vitro and in vivo. However, optimization for present limitations still needs to be addressed. In this work, we investigated huAR9.6-IRDye800 within a clinically relevant patient-derived xenograft model and through antibody fragmentation. Additionally, we proposed a future bioimaging perspective regarding the use of huAR9.6 antibody fragments and dye-encapsulated silica nanoparticles for the generation of a polyvalent nanoparticle.
Rights
The author holds the copyright to this work and any reuse or permissions must be obtained from the author directly.
Recommended Citation
Ehrhorn, Evie, "Optimization of the Near-Infrared Fluorescence Probe: HuAR9.6-IRDye800 for Fluorescence-Guided Surgery in Pancreatic Cancer" (2026). Theses & Dissertations. 1075.
https://digitalcommons.unmc.edu/etd/1075