Date of Degree

2-2020

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor

Brian M. Zeglis

Committee Members

Lynn C. Francesconi

Donna McGregor

Subject Categories

Biochemistry | Chemistry | Radiochemistry

Keywords

Positron emission tomography, near-infrared fluorescence Imaging, click chemistry, bioconjugation, cancer

Abstract

The high specificity and affinity of antibodies make them attractive for developing drugs to diagnose and treat cancer. The overarching goal of this work is to explore the synthesis and use of antibody-based imaging agents in preclinical models of cancer. This work can be described as two-fold. In the first part, we investigated how the use of a glycans-specific bioconjugation strategy affects Fc gamma RI binding and why it results in improved in vivo performance of immunoconjugates. To do so, we used the clinically relevant positron emission tomography (PET) imaging agent, 89Zr-DFO-pertuzumab, in mouse models of human breast cancer. In the second part, we developed two imaging agents for ovarian cancer, 89Zr-DFO-AR20.5 for PET and ssB43.13-IR800 for near-infrared fluorescence imaging and evaluated their in vivo performance in mouse models of human ovarian cancer. With this body of work, we hope to demonstrate the potential of antibodies as effective imaging agents for cancer.

This work is embargoed and will be available for download on Monday, July 20, 2020

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