Advisory Committee Chair
Benjamin Larimer
Document Type
Dissertation
Date of Award
2024
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Positron emission tomography (PET) imaging agents play a transformative role in personalized medicine through their application in disease diagnosis and immunotherapy monitoring, focusing on chemokine receptors, TH1-activated immune cells, and tuberculosis (TB) diagnostics. In immuno-oncology, accurately assessing TH1-activated immune cells in the tumor microenvironment (TME) is vital for evaluating cancer immunotherapy efficacy. Chemokine receptors, crucial in cellular signaling and inflammatory reactions, play a significant role in TH1 responses, thus serving as a potential area of interest in elucidating these anti-tumor responses. Through our work a novel CXCR3-targeting immunoPET probe, [89Zr]DFO-αCXCR3, was developed to detect and quantify these cells. This probe demonstrated increased tracer accumulation in treated tumors, indicating a heightened presence of CXCR3+ cells, and inversely correlated with tumor size. Our findings underscored the probe’s potential as a biomarker in monitoring immunotherapy response and guides future CXCR3-targeted PET imaging probe development for clinical application. Additionally, these approaches were extended to applications in specific targeting biomarkers of infectious disease. Our studies introduced [89Zr]-DFO-αMtb, a PET imaging probe targeting the Ag85B protein of Mtb, aimed at improving TB diagnosis accuracy. The probe showed high binding affinity to Ag85B and specific localization to Ag85B-containing sites in a C57BL/6 mouse model, highlighting its potential in differentiating active TB sites. This advancement represents a promising step in TB diagnostics, with future studies needed for validation and clinical exploration. Overall, our investigations highlight the potential of PET imaging in providing detailed insights into disease mechanisms and treatment responses, paving the way for more accurate disease diagnosis and effective monitoring of immunotherapy in cancer and infectious diseases.
Recommended Citation
Hunter, Chanelle, "Diagnostic Imaging Approaches: Pet Imaging In Monitoring Immune Responses In Oncology And Tuberculosis" (2024). All ETDs from UAB. 3852.
https://digitalcommons.library.uab.edu/etd-collection/3852