Abstract
Cancer remains a major cause of morbidity and mortality despite significant advances in detection and treatment. Chemotherapies with intolerable side effects that are highly detrimental to quality-of-life remain the standard of care for many patients. Molecularly targeted cancer imaging offers a window into underlying tumor biology and can support the use of individualized targeted therapies to spare patients from harsh or excessive treatments. Tumors consist of a complex mixture of resident and infiltrating cells as well as extracellular components, collectively known as the tumor microenvironment (TME), which plays a critical role in supporting, protecting, and enabling cancer cells to escape treatment. As the TME is increasingly recognized for modulating cancer progression, molecular imaging approaches to understand the TME hold great promise to provide a fuller picture of disease state and non-invasively aid in optimized treatment planning. In this dissertation, we explore optical imaging approaches to understand the TME and cancer-stroma relationships. Optical imaging methods are advantageous for biomedical applications given the rapid and sensitive signal detection and the innocuous nature of light. Motivated by the goal of non-invasively understanding the TME, we focused on the development of fluorescent contrast agents targeted to a variety of TME components (malignant cells, stromal cells, and extracellular matrix) that emit light in the near-infrared (NIR) spectral window, providing access to deeper tissues than visible probes. We investigated these interactions using both fluorescence intensity and lifetime imaging modalities in cellular and murine models of cancer featuring TME elements that drive patient outcomes. These studies demonstrate NIR fluorescence imaging can provide an understanding of cancer beyond a single feature of malignant cells, which has thus far been the dominant approach for cancer molecular imaging. Furthermore, imaging cancer cells and cancer-associated fibroblasts with differentially targeted NIR probes that have similar spectral profiles but distinct fluorescence lifetimes enabled concurrent detection and delineation of tumor and stromal cells. This work lays a strong foundation for multiplexed simultaneous molecular imaging of malignant cells and their microenvironment to provide more complete tumor detection and an understanding of dynamic changes in the TME as is needed to guide personalized therapy.
Committee Chair
Samuel Achilefu
Committee Members
Mikhail Berezin, Gregory Lanza; Katherine Weilbaecher; Monica Shokeen; Sheila Stewart
Degree
Doctor of Philosophy (PhD)
Author's Department
Biology & Biomedical Sciences (Biochemistry)
Document Type
Dissertation
Date of Award
4-24-2026
Language
English (en)
DOI
https://doi.org/10.7936/xtgn-dd53
Author's ORCID
https://orcid.org/0000-0001-8749-4063
Recommended Citation
Michie, Megan Suzanne, "Development and Applications of Optical Imaging Approaches for the Tumor Microenvironment" (2026). Arts & Sciences Graduate Student Theses and Dissertations. 3814.
The definitive version is available at https://doi.org/10.7936/xtgn-dd53