Advisory Committee Chair
Suzanne E Lapi
Advisory Committee Members
Eugenia Kharlampieva
William Placzek
David Schneider
Sadanandan Velu
Document Type
Dissertation
Date of Award
2023
Degree Name by School
Doctor of Philosophy (PhD) College of Arts and Sciences
Abstract
Positron emission tomography (PET) is a form of molecular imaging that allows for a noninvasive assessment of physiologic information by utilizing radioactive contrast agents. Tumor-associated macrophages (TAMs) are large phagocytic cells that play numerous roles in cancer biology and are an important component of the relationship between immune system response and tumor progression. Macrophages are broadly classified into two main groups with differing roles in immune defense and immune surveillance: classically activated macrophages (M1-like) and alternatively activated macrophages (M2-like). TAMs can influence chemoresistance, immune regulation, tumor initiation, and tumor growth, both directly and indirectly, and the presence of TAMS can lead to a poor clinical prognosis in a variety of human cancers. The peptide, RP832c, targets the Mannose Receptor (CD206) expressed on M2-like macrophages and is cross-reactive to both human and murine CD206. Additionally, it exhibits therapeutic properties through its ability to shift the population of tumor-associated macrophages (TAMs) from M2-like (pro-tumor) towards a M1-like phenotype (antitumor). Moreover, RP832c has shown promise in the inhibition of tumor resistance in PD-L1 unresponsive melanoma murine iv models and demonstrated the inhibition of bleomycin induced pulmonary fibrosis through interactions with CD206 macrophages. Our work aimed to develop a novel CD206 PET imaging probe based on RP832c, as a direct, non-invasive method for the assessment of TAMs in mouse models of cancer. We developed and evaluated [68Ga]RP832c in syngeneic murine models of colon and breast cancer showcasing high radiochemical yields, high binding to CD206, and apparent uptake in tumor and CD206 expressing organs. In addition, we explored the effects of increasing the injected mass of RP832c displaying that a higher mass injection leads to longer circulating times and changes in the macrophage profile. Moreover, we explored imaging of the mannose receptor (CD206) expressed on M2 macrophages in response to treatment with a combination therapy of anti-CTLA-4 and anti-PD-1 in syngeneic mouse models of colon cancer using [68Ga]RP832c longitudinal imaging studies. We showed that [68Ga]RP832c tumor imaging could have predictive qualities for response to treatment. Future work will aim to expand the research of [68Ga]RP832c by optimizing the probe in regard to stability and binding affinity, exploring its use in other models of cancer and disease states, and preparing for clinical translation.
Recommended Citation
Parker, Candace Ciera, "Characterization and Application of Radiolabeled Peptides for PET Imaging of CD206 Positive Macrophages in Cancer" (2023). All ETDs from UAB. 387.
https://digitalcommons.library.uab.edu/etd-collection/387
