All ETDs from UAB

Advisory Committee Chair

Anna Sorace

Advisory Committee Members

Anita Hjelmeland

Douglas Hurst

Troy Randall

Jason Warram

Document Type

Dissertation

Date of Award

2022

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Imaging is a primary component of cancer care and aids in diagnosing, response assessment, and monitoring. Molecular imaging techniques provide visualization of unique tumor biology that can be used to personalize treatment. Key features of an effective biomarker are sensitivity, specificity, and ability to provide clinical value beyond that of other types of information already available at the time of diagnosis. For particularly heterogeneous cancer subtypes, such as glioblastoma (GBM) and triple negative breast cancer (TNBC), reliable biomarkers can be challenging to identify and there are few tar-getable receptors for therapy. Our findings demonstrate that quantifying tumor EGFR (panitumumab-IRDye800CW), granzyme B ([68Ga]-GZP- PET), and hypoxia ( [18F]-flu-oromisonidazole) can be used to tumor detection and assessment of tumor response. Using a fluorescently linked targeted antibody for epidermal growth factor receptor shows potential for intraoperative detection of GBM. Improved margin definition and surgical resection with advanced imaging has the potential to improve surgical outcomes and survival in patients with GBM. The advanced positron emission tomography (PET) techniques employed in our studies provide standard uptake values of radiotracers for effector iv cell activation and hypoxia in the tumor microenvironment. Noninvasive PET imaging can provide data on the TNBC tumor microenvironment, specifically intratumoral effector cell activation and hypoxia, predicting response to immunotherapy plus chemotherapy. These findings on the underlying biological changes that occur within tumors pro-vide response kinetics that can aid in personalizing anti-cancer medicine. Use of clinically available advanced imaging techniques promises to improve outcomes of surgical tumor resection for GBM and aid in stratifying individual TNBC tumors to predict immunotherapy response early in the course of treatment.

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