Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in the world and the liver is a common site of metastases from other primary neoplasms. Many patients are not surgical candidates. Radioembolization is an intra-arterial therapy delivering high doses of radiation emitted from microspheres infused selectively into the tumor feeding arteries. These microspheres land in the tumor microcirculation and deposit radiation to the tumor tissues. Over the past ten years, radioembolization has become part of the treatment guidelines for unresectable HCC, liver-dominant metastatic colorectal cancer, and neuroendocrine liver metastases, and it is often used in the salvage setting for patients with hepatic malignancy progressing on other therapies. The overarching goal of the thesis work was to advance the basic science of 90Y radioembolization based on existing clinical needs to ultimately improve patient outcomes. This included 1) setup of pre-clinical laboratory to study radioembolization, 2) optimization of radioembolization protocols in research animals, 3) validation of 90Y PET/CT imaging techniques to monitor microsphere delivery and dosing, 4) blood oxygen-level dependent (BOLD) imaging and evaluation of tumor biology and physiology after radioembolization in the VX2 rabbit model at a fixed dose of 50 Gy, 5) evaluation of normal tissue pathology (fibrosis, atrophy) and biology (hepatocyte proliferation, microvessel density, stellate cell activation) in rats after 90Y radiation lobectomy at clinically relevant dosing from 150 to >4,000 Gy, and 6) development of new yttrium microsphere compositions for combination therapy with electromagnetic hyperthermia.
|Advisor:||Larson, Andrew C., Markl, Michael|
|Commitee:||Carroll, Timothy J., Kim, Dong-Hyun, Lewandowski, Robert J., Woloschak, Gayle E.|
|School Location:||United States -- Illinois|
|Source:||DAI-B 78/02(E), Dissertation Abstracts International|
|Subjects:||Biomedical engineering, Medical imaging, Oncology|
|Keywords:||Fibrosis, Imaging, MRI, PET/CT, Radioembolization, Yttrium-90|
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