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DESIGN AND EVALUATION OF NOVEL CONTRAST AGENTS FOR MR MOLECULAR IMAGING OF CANCER

Han, Zheng
http://rave.ohiolink.edu/etdc/view?acc_num=case149139348682434

Abstract Details

2017, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Magnetic resonance imaging (MRI) is a favorable imaging modality for cancer diagnosis due to its high soft tissue resolution and absence of ionizing radiation. However, most cancers are heterogeneous and existing MRI characteristics are insufficient to precisely delineate tumor aggressiveness for accurate prediction of clinical outcomes. MR molecular imaging aims at mining signatures that are reflections of cellular or subcellular processes in cancer, thereby uncovering hallmarks closely correlated to cancer proliferation, progression and metastasis. In this regard, contrast agents that differentially generate imaging contrast according to tumor aggressiveness is urgently needed. This dissertation is focused on developing novel contrast agents capable of probing the aggressiveness of prostate and breast cancers. Prostate cancer and breast cancer represent the leading causes of morbidity and mortality in men and women, respectively. In addition to the relatively low detection sensitivity, diagnosis of both cancers are suffering from high false-positive rates using current diagnostic techniques. In this work, extradomain-B fibronectin (EDB-FN), an abundant tumor microenvironment molecule exclusively expressed in aggressive tumors, is used as the biomarker. Peptide ligands were developed to specifically target EDB-FN, which were subsequently used to construct a library of gadolinium-based contrast agents. Our results indicate that the contrast agents developed in this work can potentially improve the sensitivity of MRI in detecting malignant cancers, lowering non-specific detection of indolent tumors and reducing gadolinium toxicity. Considering the huge unmet clinical need for accurate risk stratification and reducing overtreatment, this technology hold promise to be incorporated into clinical practice to achieve better diagnostic accuracy and treatment planning. This dissertation is divided into six chapters. Chapter 1 gives an overview of the clinical need for a non-invasive imaging modality for accurate stratification of prostate cancer and breast cancer. EDB-FN as a biomarker for cancer imaging is discussed. Chapter 2 describes the screening of peptide ligands specific for EDB-FN. Chapter 3 and Chapter 4 describe molecular imaging of prostate cancer and breast cancer, respectively, based on EDB-targeting contrast agents. Chapter 5 demonstrates imaging of triple negative breast cancers and metastases with EDB-targeting contrast agents. Chapter 6 is a summary of current work and future directions.
Zheng-Rong Lu (Advisor)
Nicole Steinmetz (Committee Chair)
William Schiemann (Committee Member)
Julian Kim (Committee Member)
227 p.
Biomedical Engineering

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Citations

  • Han, Z. (2017). DESIGN AND EVALUATION OF NOVEL CONTRAST AGENTS FOR MR MOLECULAR IMAGING OF CANCER [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case149139348682434

    APA Style (7th edition)

  • Han, Zheng. DESIGN AND EVALUATION OF NOVEL CONTRAST AGENTS FOR MR MOLECULAR IMAGING OF CANCER. 2017. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case149139348682434.

    MLA Style (8th edition)

  • Han, Zheng. "DESIGN AND EVALUATION OF NOVEL CONTRAST AGENTS FOR MR MOLECULAR IMAGING OF CANCER." Doctoral dissertation, Case Western Reserve University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case149139348682434

    Chicago Manual of Style (17th edition)

case149139348682434
368
© 2017, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.