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Full text release has been delayed at the author's request until August 16, 2026

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Therapeutic Development and MR Molecular Imaging for Treatment Monitoring of Pancreatic Ductal Adenocarcinoma

Laney, Victoria Esther Ayuk
http://orcid.org/0000-0003-1188-6591
http://rave.ohiolink.edu/etdc/view?acc_num=case1717779559152653

Abstract Details

2024, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in both diagnosis and treatment due to its aggressive nature and limited therapeutic options. Currently, highly sensitive imaging tools for assessing disease progression and tumor invasion are lacking, exacerbating issues with detection and therapeutic planning. The tumor microenvironment of PDAC plays a substantial role in determining tumor progression and makes staging difficult by establishing pre-metastatic niches. Magnetic resonance molecular imaging (MRMI) is a technique that employs contrast agents targeted to cancer-associated biomarkers. Previously, our lab developed a gadolinium contrast agent targeted to fibronectin for detecting and diagnosing cancerous lesions. In this study, we employed MRMI targeting the oncofetal protein EDB-FN, which is overexpressed in tumors in accordance with stage and grade, to monitor immunotherapies in a mouse model of PDAC. By leveraging the complex tumor microenvironment and targeting fibronectin, a known regulator of PDAC progression, MRMI was able to monitor tumors. Tumors were treated with gene therapy aimed at regulating fibronectin expression, validating that tuning fibronectin and EDB-FN produces discernible changes in MRMI signal. Additionally, in immunotherapy studies, MRMI predicted therapeutic outcomes in mice based on enhancement patterns observed during early treatment phases with novel immunotherapeutic regimens and saline controls. Correlations between signal intensity and changes in tumor response following therapy were identified, enabling classification of mice into responders and non-responders based on immunological studies and histological analysis. These findings demonstrate the potential of MRMI for immunosurveillance in PDAC. It also highlights its ability to non-invasively assess immunotherapy response, thus addressing critical challenges in PDAC management. In doing so, we have built upon existing literature and established EDB-FN-based MRMI as a tool for PDAC therapeutic monitoring.
Zheng-Rong Lu, PhD (Advisor)
David Wilson, PhD (Committee Chair)
Dan Ma, PhD (Committee Member)
Li Lily Wang, PhD (Committee Member)
Jordan Winter, MD (Committee Member)
Biomedical Engineering; Biomedical Research; Medical Imaging; Oncology
Molecular imaging, onco-immunology, pancreatic cancer, gene therapy, treatment monitoring

Recommended Citations

Citations

  • Laney, V. E. A. (2024). Therapeutic Development and MR Molecular Imaging for Treatment Monitoring of Pancreatic Ductal Adenocarcinoma [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1717779559152653

    APA Style (7th edition)

  • Laney, Victoria. Therapeutic Development and MR Molecular Imaging for Treatment Monitoring of Pancreatic Ductal Adenocarcinoma. 2024. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1717779559152653.

    MLA Style (8th edition)

  • Laney, Victoria. "Therapeutic Development and MR Molecular Imaging for Treatment Monitoring of Pancreatic Ductal Adenocarcinoma." Doctoral dissertation, Case Western Reserve University, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=case1717779559152653

    Chicago Manual of Style (17th edition)

case1717779559152653
© 2024, some rights reserved.Creative Commons License Therapeutic Development and MR Molecular Imaging for Treatment Monitoring of Pancreatic Ductal Adenocarcinoma by Victoria Esther Ayuk Laney is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.