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Positron Emission Tomography Imaging of Hepatocellular Carcinoma with Radiolabeled Choline

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Positron Emission Tomography Imaging of Hepatocellular Carcinoma with Radiolabeled Choline POSITRON EMISSION TOMOGRAPHY IMAGING OF HEPATOCELLULAR CARCINOMA WITH RADIOLABELED CHOLINE By YU KUANG Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Dissertation Adviser: Zhenghong Lee, Ph.D. Department of Biomedical Engineering CASE WESTERN RESERVE UNIVERSITY May, 2009 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of _____________________________________________________ candidate for the ______________________degree *. (signed)_______________________________________________ (chair of the committee) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. To my parents 献给我亲爱的父母 ii Table of Contents Table of Contents ....................................................................................................................... i List of Tables ........................................................................................................................... xi List of Figures ......................................................................................................................... xii Acknowledgments................................................................................................................... xv List of Abbreviations ............................................................................................................. xvi Abstract ................................................................................................................................ xviii Chapter 1 Introduction .............................................................................................................. 1 1.1 Molecular Imaging of Cancer .................................................................................... 1 1.1.1 Positron emission tomography for cancer imaging ................................................. 1 1.1.2 Molecular imaging modalities ................................................................................. 3 1.1.3 Positron emission tomography imaging for hepatocellular carcinoma .................... 7 1.2 Basic Principle of Positron Emission Tomography ................................................... 8 1.2.1 Positron emission and annihilation ..................................................................... 8 1.2.2 511 keV photon interactions in matter .............................................................. 10 1.2.2.1 Compton scattering ....................................................................................... 10 1.2.2.2 Rayleigh scattering........................................................................................... 12 1.2.2.3 Photoelectric effect .......................................................................................... 12 1.2.3 Data collection .................................................................................................. 13 i 1.2.3.1 Coincidence detection ...................................................................................... 13 1.2.3.2 Electronic timing window ................................................................................ 14 1.2.3.3 Time-of-flight .................................................................................................. 14 1.2.4 Detectors and scanner design ............................................................................ 15 1.2.4.1 Scintillation crystals ......................................................................................... 15 1.2.4.2 Dead time ......................................................................................................... 17 1.2.4.3 PET/CT ............................................................................................................ 18 1.2.4.4 Collimation ...................................................................................................... 18 1.2.5 LORs and projection data ................................................................................. 19 1.2.5.1 Lines of response (LORs) ................................................................................ 19 1.2.5.2 Organization of data ......................................................................................... 20 1.2.5.3 Projections and sinograms ............................................................................... 21 1.2.6 Image reconstruction ......................................................................................... 22 1.2.6.1 Forward problem .............................................................................................. 22 1.2.6.2 Radon transform............................................................................................... 22 1.2.6.3 Analytical reconstruction ................................................................................. 23 1.2.6.3.1 Simple backprojection ............................................................................... 23 1.2.6.3.2 Filtered backprojection (FBP) ................................................................... 24 1.2.6.4 Iterative reconstruction .................................................................................... 24 1.2.6.4.1 Five basic steps.......................................................................................... 24 ii 1.2.6.4.2 Maximum-likelihood expectation-maximization ...................................... 25 1.2.7 Attenuation correction ........................................................................................... 27 1.2.8 Scatter and randoms .......................................................................................... 28 1.2.8.1 Coincidence events .......................................................................................... 28 1.2.8.2 Scatter Correction ............................................................................................ 30 1.2.8.3 Random Correction .......................................................................................... 30 1.3 Review of the literatures ............................................................................................... 31 1.3.1 Hepatitis B viral infection induced hepatocellular carcinoma ............................... 31 1.3.1.1 Chronic hepatitis B viral Infection and hepatocellular carcinoma ................... 31 1.3.1.2 Woodchuck hepatitis virus infection induced woodchuck Model of hepatocellular carcinoma ............................................................................................. 34 1.3.2 Medical imaging of hepatocellular carcinoma ....................................................... 36 1.3.2.1 Diagnosis techniques for hepatocellular carcinoma ....................................... 36 1.3.2.2 Tumor glucose metabolism and FDG-PET imaging on cancer ....................... 38 1.3.2.3 Tumor-associated de novo fatty acid synthesis ............................................... 39 1.3.3 Imaging lipid synthesis in Cancer with PET .......................................................... 43 1.4 Organization of the thesis ............................................................................................. 45 Chapter 2 2-Deoxy-2-[18F]-fluoro-D-glucose Positron Emission Tomography Imaging of Hepatocellular Carcinoma ...................................................................................................... 46 2.1 Introduction ................................................................................................................... 46 iii 2.2 Materials and methods .................................................................................................. 48 2.2.1 Materials ................................................................................................................ 48 2.2.2 Animals .................................................................................................................. 48 2.2.3 Radiopharmaceuticals ............................................................................................ 49 2.2.4 Imaging protocol .................................................................................................... 49 2.2.5 Image analysis ........................................................................................................ 50 2.2.6 Histology ................................................................................................................ 51 2.2.7 Tissue excision ....................................................................................................... 51 2.2.8 Hexokinase activity assay ...................................................................................... 52 2.2.9 Glucose-6-phosphatase activity assay.................................................................... 53 2.2.10 Statistical Analysis ............................................................................................... 54 2.3 Results ........................................................................................................................... 54 2.3.1 PET imaging .......................................................................................................... 54 2.3.2 Enzyme activity ....................................................................................................
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