Advisor(s)
Benjamin Larimer
Committee Member(s)
Anna Sorace
Jessy Deshane
Jonathan McConathy
Zhuo Zhang
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Joint Health Sciences
Date of Award
9-9-2024
Abstract
Immune activation plays an important role in the development and treatment of tumor and fibrotic diseases. Granzyme B is a serine protease granzymes secreted by cytotoxic T cells or natural killer (NK) cells, which induces target cell apoptosis. Measuring granzyme B level is a way to quantify immune activation non-invasively. [68Ga]-NOTA-GZP PET imaging was applied in 4T1 breast cancer mouse model and LLC non-small cell lung cancer mouse model after treated with combination of 12 Gy irradiation and dual checkpoint inhibitors. There was a tumor growth and metastasis inhibition in the combination treatment group. The uptake of [68Ga]-NOTA-GZP on day 9 can predict treatment response in both mouse models. In addition, we expanded [68Ga]-NOTA-GZP to bleomycin induced pulmonary fibrosis mouse model. The uptake of [68Ga]-NOTA-GZP was significantly higher in bleomycin mice compared to the healthy mice in the early stage of inflammation (seven days after bleomycin instillation), while there was no difference between bleomycin mice and healthy mice on day 14 and day 21. Moreover, we demonstrated that Pirfenidone can decrease the inflammation level and it can be quantified by [68Ga]-NOTA-GZP PET imaging. Another essential cytokine during fibrosis development is tumor growth factor beta 1 (TGFβ1). We developed a PET probe, [89Zr]-DFO-TGFβRII, which can target TGFβ1 non-invasively. Our results showed that the uptake of [89Zr]-DFO-TGFβRII increased dur-ing the development of the pulmonary fibrosis in mouse model. There was a significant dif-ference between bleomycin mice and healthy mice as early as day 14. The new application of [68Ga]-NOTA-GZP and novel development of [89Zr]-DFO-TGFβRII can both provide non-invasive methods to quantify immune activation in cancer and pulmonary fibrosis, which could help understand the dynamic changes of immune activation and help stratification and further treatment.
ProQuest ID
Recommended Citation
Zhang, Yujun, "Non-Invasive Pet Imaging Probes For Immune Activation And Fibrosis In Cancer And Pulmonary Fibrosis" (2024). All ETDs from UAB. 7567.
https://digitalcommons.library.uab.edu/etd-collection/7567
