Advisor(s)

Suzanne Lapi

Committee Member(s)

Anna Sorace
Benjamin Larimer

Document Type

Thesis

Date of Award

1-27-2026

Degree Name

Master of Science (MS)

School

Joint Health Sciences (Interdisciplinary)

Department

Joint Health Sciences

Abstract

Trophoblast cell surface antigen 2 (Trop2) is closely related to the development and progression of triple-negative breast cancers (TNBC) and is also being investigated as a pan-cancer biomarker. Trop-2 tumorigenesis is mediated by the calcium ion signaling pathways. By accurately predicting and targeting Trop-2 for immunotherapy, precision therapy is crucial. Trop-2 is overexpressed in tumor tissues compared to normal tissues, which makes it a promising molecular target for cancer-targeted therapy. This thesis reports the development and preclinical evaluation of two novel Trop-2-specific radiopharmaceutical tracers derived from the clinically approved antibody-drug conjugate Sacituzumab Govitecan (SG): a full antibody drug conjugate-based tracer and a Fab fragment-based tracer. SG fragmentation was performed using immobilized papain protease, separating Fab and Fc fragments. The fragments were then subsequently purified using Protein A agarose. SG and Fab fragments were conjugated with DFO and radiolabeled with Zirconium-89. High radioactive purity (>95%) tracers exhibited specific binding and uptake in Trop-2 high-expressing TNBC cell lines (MDA-MB-468) compared to Trop-2 low-expressing lines (MDA-MB-231). In vivo PET/CT imaging in xenograft mouse models demonstrated selective tumor localization with distinct pharmacokinetics between the SG and Fab fragment tracers. This work validates the feasibility of using 89Zr-DFO-Sacituzumab Govitecan-derived probes for imaging of Trop-2 expression, paving the way for improved diagnostics, patient stratification, and monitoring of Trop-2-targeted therapies in TNBC. The findings fill a critical gap in precision oncology, supporting future translational and clinical applications of Trop-2 PET imaging.

Keywords

Fab Fragment;PET;Sacituzumab Govitecan;triple-negative breast cancer;Trop-2

ProQuest Publication Number

32286448

ISBN

9798273381131

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