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Degree

Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering, 2009.

Abstract

Hepatocellular Carcinoma (HCC) is one of the most common malignancies throughout the world and its five-year survival rate has been dismal (5%). The carcinogenesis is frequently associated with the metabolic changes that precede the morphological changes. Therefore, a non-invasive, fast, quantitative technique for detection of HCC is much needed. Positron emission tomography (PET), a molecular imaging technique, holds particular promise for diagnostic imaging of neoplasms. The focus of this thesis is on the diagnostic utility of PET metabolic imaging on HCC and the mechanisms underlying the imaging using radiolabeled choline (CHOL) as the tracer. (1) Many cancers display a high rate of aerobic glycolysis, a phenomenon that is exploited by 2-Deoxy-2-[¹⁸F]-fluoro-D-glucose (FDG) PET imaging for the detection of tumors. Up-regulation of glycolytic metabolism plays a role in tumor progression by contributing to tumor growth or survival. In this study, the usefulness of FDG-PET for HCC was investigated. The study addressed the correlation between FDG-PET images with pathologic types of HCC. The overall sensitivity of FDG-PET in the detection of HCC is low (50-55%). This can be explained by the wide variability in enzyme activity in the individual HCC. In well-differentiated HCC, FDG metabolism may be similar to that of the surrounding liver, leading to a false negative result, while higher sensitivity was reported in poorly differentiated HCC. (2) Increased lipid synthesis is required by a growing tumor cell to synthesize membranes and lipid-modified signaling molecules. The radiolabeled choline (CHOL) was used to probe lipid synthesis in HCC. In this study, PET/CT imaging was correlated with metabolites analysis in vivo and in vitro, which helps to explain the heterogenous uptake of radiolabeled CHOL in HCC. Transport and phosphorylation of CHOL are responsible for the tracer accumulation during [¹¹C]-CHOL PET imaging in well-differentiated HCC. Moreover, basal oxidation and phosphorylation activities in surrounding hepatic tissue contribute to the background signal seen in [¹¹C]-CHOL PET images. Furthermore, PET imaging of lipid synthesis with radiolabeled CHOL is useful in well-differentiated HCC that is not FDG avid. PET/CT imaging with radiolabeled CHOL could thus be a very promising diagnostic tool in patients with suspicious liver masses.

Subject Headings

Biochemistry; Engineering; Health; Radiology; Scientific imaging

Keywords

Hepatocellular Carcinoma; Positron Emission Tomography (PET); [¹¹C]-choline; Molecular imaging; FDG; Cancer Metabolism; Transport mechanism; Phosphatidylcholine synthesis; Lipids; High performance liquid chromatography

Committee / Advisors

Zhenghong Lee, Ph.D. (Advisor)
David Wilson, Ph.D. (Committee Chair)
Thomas Kelley, Ph.D. (Committee Member)
Xin Yu, Sc.D. (Committee Member)

Pages

226p.

Document number: case1238781224
Permalink: http://rave.ohiolink.edu/etdc/view?acc_num=case1238781224

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