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University of Huddersfield Repository Ratcliffe, Naomi Potential of a compact low energy proton accelertor for medical applications Original Citation Ratcliffe, Naomi (2014) Potential of a compact low energy proton accelertor for medical applications. Doctoral thesis, University of Huddersfield. This version is available at http://eprints.hud.ac.uk/23711/ The University Repository is a digital collection of the research output of the University, available on Open Access. Copyright and Moral Rights for the items on this site are retained by the individual author and/or other copyright owners. 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For more information, including our policy and submission procedure, please contact the Repository Team at: [email protected]. http://eprints.hud.ac.uk/ POTENTIAL OF A COMPACT LOW ENERGY PROTON ACCELERTOR FOR MEDICAL APPLICATIONS NAOMI RATCLIFFE A thesis submitted to the University of Huddersfield in partial fulfilment of the requirements for the degree Doctor of Philosophy The University of Huddersfield in collaboration with Siemens plc May 2014 ABSTRACT This thesis explores the potential of a compact low energy (<10MeV) proton accelerator for medical applications such as the production of neutrons for cancer neutron therapy and the production of SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) radioisotopes. During the course of this study the simulation code GEANT4 was used to study yields of these neutrons and isotopes from the typically low threshold high cross‐section (p,n) reactions. Due to the limits of the current models within GEANT4 some development of a new data‐driven model for low energy proton interactions was undertaken and has been tested here. This model was found to be suitably reliable for continued study into the low energy production of positron emitting, PET, isotopes of copper and gallium as replacements for the main SPECT isotope technetium‐99m. While 99mTc is currently the most popular radioisotope being used in over 90% of the worlds nuclear medicine diagnostic procedures supply is under threat by the impending shut down of the current reactor based sources Simulations of both thin and thick targets were carried out to study the potential of low energy production of these isotopes. The final activity of the radioisotopes after irradiation of these targets produced by the simulations has been shown here to be sufficient for multiple doses. The useable activity is dependent on the efficiency of the extraction process and the time between irradiation and administration. 2 Acknowledgements Acknowledgment of the funding for this work from the EPSRC and Siemens plc and the use of the resources of the University of Huddersfield. Firstly a special thank you to my supervisor Prof. Bob Cywinski for all of his time and support. I have grown both professionally and personally from his guidance and insights. I have to thank Drs. A. & C. Bungau for all their work on GEANT4 without them there would still not be a working model. I would also like to thank P. Beasley and O. Heid of Siemens for their input into this work. I have been privileged to be the first student through the IIAA at the University of Huddersfield. This has given me a special opportunity to have unlimited access to pick the brains of international reputations such as Prof. Roger Barlow, Prof. Becky Seviour(who put me in touch with this project in the first place), Prof. Sue Kilcoyne and Prof. Rob Edgecock. Each of these people have supported me throughout our time together and have brightened my day when I needed it most, even if they could not give me the answers that were eluding me. And of course a special mention to all the other students in our group that joined me over the years, especially to my office mates Anna Kolano and Simon Albright. What a pair, thank for the laughs and making everyday so interesting. Finally my family for supporting me through all the choices that led me here. 3 Copyright Statement i. The author of this thesis (including any appendices and/or schedules to this thesis) owns any copyright in it (the “Copyright”) and s/he has given The University of Huddersfield the right to use such Copyright for any administrative, promotional, educational and/or teaching purposes. ii. Copies of this thesis, either in full or in extracts, may be made only in accordance with the regulations of the University Library. Details of these regulations may be obtained from the Librarian. This page must form part of any such copies made. iii. The ownership of any patents, designs, trademarks and any and all other intellectual property rights except for the Copyright (the “Intellectual Property Rights”) and any reproductions of copyright works, for example graphs and tables (“Reproductions”), which may be described in this thesis, may not be owned by the author and may be owned by third parties. Such Intellectual Property Rights and Reproductions cannot and must not be made available for use without the prior written permission of the owner(s) of the relevant Intellectual Property Rights and/or Reproductions. 4 Contents 1. INTRODUCTION 8 1.1 Boron Neutron Capture Therapy 12 1.1.1 Introduction 12 1.1.2 Trials 14 1.1.3 Neutron Production 15 1.1.4 Targetry 17 1.1.5 The Basis of the Current Study 19 1.2 Radioisotopes For Imaging And Therapy 20 1.2.1 Introduction 20 1.2.2 Production of Radioisotopes Using Nuclear Reactors 22 1.2.3 Generator Technology 23 1.2.4 Modern Nuclear Medicine 25 1.2.4.1 SPECT 25 1.2.4.2 PET 27 1.2.5 The 99mTc Crisis 28 1.2.6 The Role of This Research Programme 29 2. GEANT4 31 2.1 Introduction 31 2.2 Structure 32 2.3 Creating A GEANT4 Simulation 34 2.3.1 Detector Construction 34 2.3.2 Physics List 36 2.3.3 Primary Generator Action 37 2.3.4 User Run Action 38 2.3.5 User Event Action 38 2.3.6 User Stacking Action 38 2.3.7 User Tracking Action 38 2.3.8 User Stepping Action 39 2.3.9 Other Files 39 2.3.9.1 Macros 39 2.3.9.2 Executable 40 2.4 Physics Models 40 2.4.1 QGSP_BERT_HP 41 2.4.2 QGSP_BIC_HP 44 2.4.3 QGSP_BIC_PHP 45 2.5 Validation 45 3. BNCT 47 3.1 Initial GEANT4 Benchmarking Process 47 3.2 Results 48 3.2.1 Uncertainties 49 3.2.2 Experimental Results 49 3.2.3 QGSP_BERT_HP 50 3.2.4 QGSP_BIC_HP 52 3.2.5 QGSP_BIC_PHP 54 5 3.3 Further Simulation Studies: Effect of Target Thickness 55 3.3.1 Simulations 55 3.3.2 Results 56 3.4 Further Simulation Studies: Angular Distribution 57 3.4.1 Simulation 58 3.4.2 Results 59 3.5 Conclusions 60 4. GEANT4 BENCHMARKING FOR MEDICAL ISOTOPE PRODUCTION 61 4.1 Introduction 61 4.2 Copper‐64 62 4.2.1 Simulations 63 4.2.2 Results 63 4.3 Zirconium‐89 65 4.3.1 Background 65 4.3.2 Results 66 4.4 Iodine‐123 67 4.4.1 Background 67 4.4.2 Results 68 4.5 Conclusions 69 5. LOW ENERGY PRODUCTION OF 99MO/99MTC 70 5.1 Canadian Light Source: The Electron Approach 71 5.2 TRIUMF: The Proton Approach 72 5.3 Low Energy Production of 99mTc 73 5.3.1 Direct Production 74 5.3.2 Generator Production 74 5.4 Further Benchmarking Studies 75 5.5 Conclusions 77 6. COPPER ISOTOPES FOR MEDICAL APPLICATIONS 80 6.1 Background 80 6.2 Copper Isotopes for Targeted Radiotherapy 80 6.3 Copper Isotopes for Nuclear Imaging: 62Cu 81 6.3.1 Background 81 6.3.2 Low Energy Production 83 6.2.2.1 Target Thickness and Yields 84 6.2.2.2 Activity 85 6.3 Target Processing and Production 91 6.4 Copper Isotopes for Nuclear Imaging: 61Cu 92 6.4.1 Potential of 61Cu 92 6.4.2 Current Production Routes 92 6.4.3 Low Energy Production 93 6.4.3.1 Target Thickness and Yields 94 6.4.3.2 Activity 95 6.4.4 Target Processing and Production 98 6 6.5 Copper Isotopes for Nuclear Imaging: 60Cu 98 6.5.1 Potential Uses 98 6.5.2 Current Production 99 6.5.3 Low Energy Production 100 6.5.3.1 Target Thickness and Yields 100 6.5.3.2 Activity 101 6.5.4 Target Processing and Production 104 6.6 Conclusions 105 7. GALLIUM ISOTOPES FOR MEDICAL APPLICATION 107 7.1 Background 107 7.2 Current SPECT Isotope: 67Ga 107 7.2.1 Background 107 7.2.2 Current Production Routes 108 7.2.3 Low Energy Production 109 7.3 PET Isotopes: 68Ga 109 7.3.1 Applications 109 7.3.2 Current Production Routes 110 7.3.3 Low Energy Production 111 7.3.3.1 Target Thickness and Yields 112 7.3.3.2 Activity 114 7.3.4 Target Processing and Production 118 7.4 PET Isotopes: 66Ga 119 7.4.1 Background 119 7.4.2 Production Routes 119 7.4.2.1 Target Thickness and Yields 120 7.4.2.2 Activity 121 7.4.3 Target Processing and Production 125 7.5 Conclusions 125 8.