Dissertations, Theses, and Capstone Projects

Date of Degree

6-2024

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biochemistry

Advisor

Brian Zeglis

Committee Members

Melissa Deri

Prabodhika Mallikaratchy

Naga Vara Kishore Pillarsetty

Subject Categories

Animal Experimentation and Research | Biochemistry | Biological and Chemical Physics | Diagnosis | Environmental Health and Protection | Radiochemistry | Therapeutics

Keywords

positron emission tomography, imaging, radiochemistry, theranostics, antibody, microplastics

Abstract

The last half century has played witness to the onset of molecular imaging for the clinical assessment of physiological targets. While several medical imaging modalities allow for the visualization of the functional and anatomical properties of humans and living systems, few offer accurate quantitation and the ability to detect biochemical processes with low-administered drug mass doses. This limits how physicians and scientists may diagnose and treat medical issues, such as cancer, disease, and foreign agents.

A promising alternative to extant invasive procedures and suboptimal imaging modalities to assess the nature of a biological environment is the use of positron emission tomography (PET). Excitingly, the efforts of the nuclear medicine community over the past two decades have resulted in a remarkable surge in the use of PET, establishing it as a standard practice and part of routine care in hospitals and laboratories across the globe. Specifically, PET allows for the exquisite sensitive and specific detection of biomarkers with high spatial resolution and image contrast. This dissertation describes the use of PET and radionuclides for two purposes: 1) the development of novel radiopharmaceuticals for the imaging and potential therapy of cancer, and 2) the physiological assessment of environmental pollutants in living systems. Several chapters in this body of work are dedicated to the synthesis of antibody-based radiopharmaceuticals and novel site-specific bioconjugation strategies, and their promise for clinical translation for the treatment of cancer patients. On quite a different note, the use of PET in environmental science — particularly, to track micro- and nanoplastics in mammalian systems — will also be discussed. Each scientific study will contain a detailed introduction, information on the materials and methods used, an in-depth analysis of the results that is either paired with or followed by a discussion, and final conclusions. Chapters explaining the theoretical principles guiding this work and providing analyses of prior literature are included, and the future implications of each study — as well as the field as a whole — will also be examined.

Part I of this dissertation is dedicated to the use of radiotracers and molecular imaging in oncology while Part II will explore their uses in environmental science.

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