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<p> 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.</p>

Progression of Alzheimer's disease has been associated with the deposition of aggregated amyloid beta (Aβ) protein in the brain. Though first described in post-mortal tissue, the development of Aβ specific tracers for positron emission tomography (PET) permits in-vivo mapping of its distribution in the brain. One of the well-known and early-developed tracers is the Pittsburgh Compound B (PiB) (Klunk et al., 2004). However, the challenge with PiB lies in the stability of the radioisotope 11C. 11C's short half-life of only 20 minutes hinders its transportation and usage at imaging facilities that are not in close proximity with the radioisotopes manufacturer. Recently, an alternative Aβ tracer has been developed, Florbetapir (Wong et al, 2010.), with a half-life of 110 minutes that should allow wider accessibility to imaging sites while improve the detection of Aβ. To define better the specificity and utility of Florbetapir, we propose to utilize existing PET data acquired with the radioactive tracer Florbetapir from the Alzheimer's disease Neuroimaging Initiative (ADNI). Our goal is to characterize the symmetry of Aβ protein deposition in the brain of patients with Alzheimer's disease. While a previous study has investigated this issue using PiB, Florbetapir has not been used. Our project will involve data post-processing by segmenting out non-brain tissues. Segmented data is then normalized by the pixel intensity and a distribution curve is created using MathCad program. In addition, we will calculate the asymmetry score for Regions of Interest. This will permit comparison of the uptakes of tracer between brain hemispheres to be made. Results from our project can provide insight into Florbetapir's binding affinity for Aβ. In addition, Florbetapir's potential as a better alternative to PiB can also be evaluated.

Despite that most vestibular schwannomas are successfully treated with radiotherapy, current follow-up protocols entail years of serial magnetic resonance imaging (MRI) scans to ensure cessation of growth. This pilot study sought to identify early predictors of radiation treatment response using a non-invasive multi-modality imaging approach. We hypothesized that by combining information acquired from dynamic contrast-enhanced MRI (DCE-MRI), diffusion tensor imaging (DTI), and L-¹¹C-methionine positron emission tomography (MET-PET) treatment response could be identified sooner than the current several year waiting period. This thesis presents the baseline MRI and MET-PET results of the pilot study acquired to-date with follow-up data to be acquired in the next six months. Baseline results suggest that DTI and DCE-MRI yield information that may be useful in identifying the response of vestibular schwannomas to radiotherapy. In particular, vestibular schwannomas display elevated mean diffusion coefficients relative to the contra-lateral cerebellum. Also, the novel use of arterial input functions derived from the anterior inferior cerebellar arteries has led to the successful implementation of DCE-MRI pharmaco-kinetic models which may be used to quantitatively monitor tumor response to radiotherapy. Furthermore, MET-PET has shown promise as a tool for evaluating response as all tumors exhibited enhancement under this modality as compared to the contra-lateral side of the brain. Single-voxel spectroscopy with 3T MRI has proven to be a poor technique with which to examine vestibular schwannomas since only two of eight spectra were acquired successfully. All of the techniques that have shown promise as investigatory tools of tumor response can potentially be implemented clinically in the near future.

Despite that most vestibular schwannomas are successfully treated with radiotherapy, current follow-up protocols entail years of serial magnetic resonance imaging (MRI) scans to ensure cessation of growth. This pilot study sought to identify early predictors of radiation treatment response using a non-invasive multi-modality imaging approach. We hypothesized that by combining information acquired from dynamic contrast-enhanced MRI (DCE-MRI), diffusion tensor imaging (DTI), and L-¹¹C-methionine positron emission tomography (MET-PET) treatment response could be identified sooner than the current several year waiting period. This thesis presents the baseline MRI and MET-PET results of the pilot study acquired to-date with follow-up data to be acquired in the next six months. Baseline results suggest that DTI and DCE-MRI yield information that may be useful in identifying the response of vestibular schwannomas to radiotherapy. In particular, vestibular schwannomas display elevated mean diffusion coefficients relative to the contra-lateral cerebellum. Also, the novel use of arterial input functions derived from the anterior inferior cerebellar arteries has led to the successful implementation of DCE-MRI pharmaco-kinetic models which may be used to quantitatively monitor tumor response to radiotherapy. Furthermore, MET-PET has shown promise as a tool for evaluating response as all tumors exhibited enhancement under this modality as compared to the contra-lateral side of the brain. Single-voxel spectroscopy with 3T MRI has proven to be a poor technique with which to examine vestibular schwannomas since only two of eight spectra were acquired successfully. All of the techniques that have shown promise as investigatory tools of tumor response can potentially be implemented clinically in the near future.

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