PhD Thesis Defense: Boyu Meng

For info on how to attend this videoconference, please email boyu.meng.TH@dartmouth.edu

"Development and translation of novel molecular imaging techniques to quantify cancer receptor expression"

Abstract

Exploiting the abnormal receptor expression profile of individual tumors with receptor-targeted drugs has emerged as an increasingly important strategy for treating cancer. Yet, low response rates in patients have hindered clinical translation of novel drugs despite increased investment in pharmaceutical research and development. In this context, the abundance of these receptors and the ability of drugs to bind to their targets are important preconditions for these therapies to be effective. Accurate quantification and monitoring of relevant biomarkers can enable a direct correlation between target drug interaction and therapeutic efficacy. However, current techniques to assess receptor availability require removal of tissue for analysis and do not explicitly report receptor availability in the native environment. To overcome these shortcomings, this thesis explores the possibility of utilizing and optimizing innovative imaging technologies to acquire molecular specific signal and quantify biological processes that are key targets in disease processes.

Specifically, the scope of this thesis focuses on:

1. noninvasive quantification of receptor availability during receptor targeted cancer therapy,
2. development of a cross-modality paired-agent imaging paradigm using clinical imaging modality, and
3. detection of cancer cell surface receptor availability in response to anti-angiogenesis therapy.

As part of these efforts, the kinetics and characteristics of the imaging agents themselves were examined using novel imaging instruments and strategies. Specifically:

1. a unique hyperspectral whole-animal fluorescence imaging cryo-macrotome was used to study biodistribution of various fluorescent agents, and to identify agents which behave similar to contrast-enhanced MRI, and
2. a receptor-specific topical staining technique for identifying tumor in the margins of fresh specimens was examined using quantum dot-labeled imaging agents.

As cancer therapy becomes more personalized, diagnostic tools can reveal important information about biological indicators specific to each patient. By investigating these biological questions, this thesis emphasizes the importance of molecular imaging technologies that could substantially impact translational efforts for new drug development, patient stratification to different treatment regimens, and regular monitoring for drug engagement during treatment.

Thesis Committee

• Scott C. Davis, PhD (Chair)
• Brain W. Pogue, PhD
• Kimberley S. Samkoe, PhD
• Kenneth M. Tichauer, PhD

Contact

For more information, contact Daryl Laware at daryl.a.laware@dartmouth.edu.