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Masterarbeit MASTERARBEIT Titel der Masterarbeit „Radiosynthesis of the DAT-PET-Tracer [18F]FE@IPCIT“ verfasst von Cornel Fink, BSc angestrebter akademischer Grad Master of Science (MSc) Wien, 2013 Studienkennzahl lt. Studienblatt: A 066 862 Studienrichtung lt. Studienblatt: Masterstudium Chemie Betreut von: assoc. Professor Dr. Wolfgang Wadsak meinen Eltern Table of Content 1 INTRODUCTION .................................................................................................................... 1 1.1 RADIOACTIVITY ............................................................................................................................ 1 1.1.1 Radioactive Decay ............................................................................................................... 1 1.1.2 Activity ................................................................................................................................. 2 1.1.3 Half-life ................................................................................................................................ 2 1.1.4 Decay Modes ....................................................................................................................... 2 1.1.4.1 Alpha (α) Radiation ................................................................................................................... 2 1.1.4.2 Beta (β) Radiation ..................................................................................................................... 3 1.1.4.2.1 β- Decay (Electron Emission) ................................................................................................ 3 1.1.4.2.2 β+ Decay (Positron Emission) ............................................................................................... 3 1.1.4.3 Electron Capture ....................................................................................................................... 4 1.1.4.4 Gamma (γ) Radiation ................................................................................................................ 4 1.1.5 Nuclides ............................................................................................................................... 5 1.1.5.1 Non-metallic Radioisotopes ..................................................................................................... 5 1.1.5.1.1 Carbon-11 ............................................................................................................................. 5 1.1.5.1.2 Fluorine-18 ........................................................................................................................... 5 1.1.5.1.3 Nitrogen-13 .......................................................................................................................... 6 1.1.5.1.4 Oxygen-15 ............................................................................................................................ 7 1.1.5.2 Metallic Radioisotopes ............................................................................................................. 7 1.1.5.2.1 Gallium-68 ............................................................................................................................ 7 1.1.5.2.2 Technetium-99m and Technetium-94m .............................................................................. 8 1.2 INSTRUMENTATION IN NUCLEAR CHEMISTRY AND NUCLEAR MEDICINE ................................................. 8 1.2.1 Production of Radioactive Isotopes ..................................................................................... 8 1.2.1.1 Cyclotron .................................................................................................................................. 8 1.2.1.2 Nuclear Reactor ........................................................................................................................ 9 1.2.1.3 Generator ................................................................................................................................. 9 1.2.2 Imaging Techniques ........................................................................................................... 10 1.2.2.1 X-ray ....................................................................................................................................... 10 1.2.2.2 Computed Tomography .......................................................................................................... 10 1.2.2.3 Magnetic Resonance Imaging ................................................................................................. 11 1.2.2.4 PET Positron Emissions Tomography and Single-photon Emission Computed Tomography . 11 1.2.2.4.1 Positron Emissions Tomography ........................................................................................ 12 1.2.2.4.2 Single-photon Emission Computed Tomography ............................................................... 12 1.2.3 Synthesis Modules ............................................................................................................. 12 I 1.2.3.1 Automated Synthesis Modules............................................................................................... 13 1.2.3.2 Manually Operated Synthesis Modules .................................................................................. 13 1.2.4 High performance liquid chromatography ........................................................................ 13 1.2.4.1 Basic Principles ....................................................................................................................... 13 1.2.4.2 Instrumentation ..................................................................................................................... 14 1.2.4.3 Analytical HPLC vs. Semi-preparative HPLC ........................................................................... 15 1.3 SYNAPTIC TRANSDUCTION ........................................................................................................... 15 1.3.1 Neurotransmitter ............................................................................................................... 16 1.3.1.1 Definition of a Neurotransmitter............................................................................................ 16 1.3.1.2 Characteristics ........................................................................................................................ 16 1.3.1.3 Classification System .............................................................................................................. 16 1.3.2 Neurotransmitter Substances (Selection) .......................................................................... 17 1.3.2.1 Catecholamines ...................................................................................................................... 17 1.3.2.1.1 Dopamine ........................................................................................................................... 17 1.3.2.1.2 Epinephrine and Norepinephrine....................................................................................... 18 1.3.2.1.3 Serotonin ............................................................................................................................ 18 1.3.3 Neurotransmitter Receptors .............................................................................................. 18 1.3.3.1 Dopamine Receptors .............................................................................................................. 19 1.3.3.2 Epinephrine and Norepinephrine Receptors .......................................................................... 19 1.3.3.3 Serotonin Receptors ............................................................................................................... 19 1.3.4 Mechanisms of Reuptake and Decomposition of Neurotransmitters ............................... 19 1.3.4.1 Neurotransmitter Transporter Sites ....................................................................................... 19 1.3.4.1.1 Dopamine Transporters ..................................................................................................... 20 1.3.4.1.2 Serotonin Transporters ...................................................................................................... 20 1.3.4.1.3 Norepinephrine Transporter .............................................................................................. 20 1.3.5 Illicit Drugs: Mechanism of Action ..................................................................................... 21 1.4 RADIOPHARMACY ...................................................................................................................... 22 1.4.1 Radiopharmaceuticals ....................................................................................................... 22 1.4.2 Characteristics and General Consideration for Radiopharmaceuticals ............................. 23 1.4.3 Effective Half-life ............................................................................................................... 24 1.4.4 Specific Activity .................................................................................................................. 24 1.5 TRACER .................................................................................................................................... 24 1.6 FROM COCAINE TO FE@IPCIT .................................................................................................... 25 1.6.1 Cocaine .............................................................................................................................
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