University of Ghana http://ugspace.ug.edu.gh PERFORMANCE EVALUATION AND CROSS-CALIBRATION OF ® CAPINTEC CRC 15R AND COMECER DOSE CALIBRATORS Presented to DEPARTMENT OF MEDICAL PHYSICS SCHOOL OF NUCLEAR AND ALLIED SCIENCES UNIVERSITY OF GHANA BY ELIAS MWAPE (10611916) IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF A MASTER OF PHILOSOPHY IN MEDICAL PHYSICS JULY, 2018 University of Ghana http://ugspace.ug.edu.gh DECLARATION This thesis is the result of research work undertaken by Mr. ELIAS MWAPE in the Department of Medical Physics, School of Nuclear and Allied Sciences, University of Ghana, under the supervision of Prof. A.K Kyere, Dr. F. Hasford and Dr. E.K. Sosu. Sign……………………………… Date…………………………… Elias Mwape (Student) Supervisor’s Declaration The preparation and presentation of this thesis were supervised in accordance with guidelines on supervision of thesis laid down by the University of Ghana. Sign…………………………… Date…………………………… Dr. F. Hasford (Principal supervisor) Sign…………………………… Date…………………………… Prof. A.K Kyere (Co-supervisor) Sign…………………………… Date…………………………… Dr. E.K .Sosu (Co-supervisor) i University of Ghana http://ugspace.ug.edu.gh DEDICATION This research work is dedicated to my lovely fiancée Violet Mbwili for the love, moral and spiritual support. It is also dedicated to my parents Brendah Kasali and Everisto Mwape for making me see the value of education. Last but not the least, dedicated also to all my friends and family especially Bishop Justine Gondwe and the Macedonia church family. ii University of Ghana http://ugspace.ug.edu.gh ACKNOWLEDGEMENTS First and foremost I give Glory, honor and adoration to God Almighty for His grace, guidance and protection throughout the course of this research study. Indeed he has being my strength and shield. I am also forever indebted to the dedicated team of supervisors Professor A.W.K. Kyere, Dr. Francis Hasford and Dr. Edem Sosu for their invaluable guidance and support rendered to me in seeing this research work to completion. Special thanks goes to my sponsor, IAEA for the financial support without which this work could not have come to a successful end. I would also like to thank all my lecturers from the Graduate School of Nuclear and Allied Sciences (SNAS) for the coursework which gave me better foundation for understanding this research work. I am also grateful to the nuclear medicine department at Korle-Bu Teaching Hospital for allowing to me to use the equipment and materials in the Department. Special thanks more especially to the nuclear medicine technologists Mr. Daniel Ashley and Mr. Adu Asimeng Sarkodie for their cooperation and support throughout the process of data collection. Special thanks to the entire Nuclear medicine unit at the University Teaching Hospital in Zambia for the encouragement and support throughout my stay in Ghana. Finally, special thanks to my friends Clement Dominic Chaphuka, Joana Otoo and Silas Chabi for their moral support and encouragements. God richly bless you all. iii University of Ghana http://ugspace.ug.edu.gh TABLE OF CONTENTS DECLARATION ....................................................................................... i DEDICATION .......................................................................................... ii ACKNOWLEDGEMENTS ..................................................................... iii TABLE OF CONTENTS ......................................................................... iv LIST OF FIGURES.................................................................................. ix LIST OF TABLES ................................................................................... xi LIST OF ABBREVIATIONS AND SYMBOLS ................................... xii ABSTRACT ........................................................................................... xiii CHAPTER ONE ....................................................................................... 1 INTRODUCTION ..................................................................................... 1 1.1 BACKGROUND ........................................................................................... 1 1.2 STATEMENT OF THE PROBLEM ............................................................ 2 1.3 OBJECTIVES OF THE STUDY .................................................................. 4 1.4 RELEVANCE AND JUSTIFICATION ....................................................... 4 1.5 SCOPE AND DELIMITATION ................................................................... 5 1.6 ORGANISATION OF THESIS .................................................................... 5 CHAPTER TWO ...................................................................................... 6 LITERATURE REVIEW ......................................................................... 6 2.1 BASIC PHYSICS OF THE DOSE CALIBRATOR ..................................... 6 iv University of Ghana http://ugspace.ug.edu.gh 2.1.1 Radioactive decay .................................................................................. 6 2.2 INTERACTION OF RADIATION WITH MATTER .................................. 8 2.2.1 Charged particle interaction with matter ................................................ 8 2.2.2 Interactions of Photons with Matter ..................................................... 10 2.2.3 Gas filled detectors ............................................................................... 13 2.2.4 The modern radionuclide calibrator ..................................................... 15 2.2.1 Absorbed dose via measurement of current or activity ........................ 17 2.3 CALIBRATION OF DOSE CALIBRATORS ............................................ 18 2.3.1 Energy-response Curves (Photons) ...................................................... 19 2.3.2 Dial value or Calibration number (NA) ................................................ 21 2.3.3 Determining dial values for Capintec dose calibrator (Capintec 2007, 2015). 22 2.4 DOSE CALIBRATOR QUALITY CONTROL TESTS ............................. 24 2.4.1 Quality Assurance and Quality Control ............................................... 24 2.4.2 Constancy check................................................................................... 25 2.4.3 Linearity of response test ..................................................................... 26 2.4.4 Accuracy test ........................................................................................ 28 2.4.5 Geometry test ....................................................................................... 28 2.4.6 Standards relating to dose calibrators .................................................. 29 2.5 SOME SOURCES OF ASSAY ERRORS .................................................. 30 2.5.1 User errors ............................................................................................ 30 2.5.2 Calibration geometry ............................................................................ 31 v University of Ghana http://ugspace.ug.edu.gh 2.5.3 Effects of an external shield ................................................................. 31 2.5.4 Effects of container material ................................................................ 32 2.5.5 Effects of impurities ............................................................................. 33 2.5.6 Drift in the electronics of the calibrator ............................................... 33 CHAPTER THREE ................................................................................. 35 MATERIALS AND METHODS ............................................................ 35 3.1 Introduction ................................................................................................. 35 3.2 MATERIALS USED FOR THIS RESEARCH .......................................... 35 3.2.1 Materials and equipment ...................................................................... 36 3.2.2 Comecer Dose Calibrator ..................................................................... 36 3.2.3 Capintec Dose Calibrator ..................................................................... 37 3.2.4 Standard radionuclide source ............................................................... 38 3.3 SOFTWARE ............................................................................................... 38 3.3.1 Microsoft Excel 2010 ........................................................................... 38 3.3.2 Minitab 16 software ............................................................................. 39 3.4 Methods ....................................................................................................... 40 3.4.1 Physical inspection ............................................................................... 40 3.4.2 Performance checks ............................................................................. 40 3.4.3 Constancy check................................................................................... 41 3.4.4 Accuracy test ........................................................................................ 42 3.4.5 Linearity test......................................................................................... 42 vi University of Ghana http://ugspace.ug.edu.gh 3.4.6 Geometry test ....................................................................................... 43 3.4.7 Contamination test ............................................................................... 44 3.4.8 Other Statistical methods ..................................................................... 45 CHAPTER FOUR ................................................................................... 46 RESULTS AND DISCUSSIONS ........................................................... 46 4.1 Quality Control ............................................................................................ 46 4.2 Daily quality control .................................................................................... 47 4.3 Constancy check .......................................................................................... 48 4.4 Relative response check .............................................................................. 49 4.5 Accuracy test ............................................................................................... 51 4.6 Linearity response ....................................................................................... 52 4.6.1 Overestimation of 99mTc assays by capintec ........................................ 55 4.6.1 Capintec electrometer inacuracy .......................................................... 56 4.6.2 Effects liner and/or dipper residual contamination .............................. 57 4.7 Geometry test .............................................................................................. 59 4.8 CHOOSING REFERENCE DOSE CALIBRATOR FOR CROSS CALIBRATION .................................................................................................... 64 4.8.1 137Cs Calibration factor (CF) ................................................................ 65 4.9 Cross-calibration curve for 99mTc assays on Capintec with Comecer as the reference dose calibrator. ...................................................................................... 67 4.9.1 Validation of 9mTc calibration curve .................................................... 69 4.10 Determination of new dial value (N ) for 99mTc and 137A Cs on Capintec ..... 70 vii University of Ghana http://ugspace.ug.edu.gh 4.10.1 99m Tc new dial value (NA) on Capintec ................................................ 71 4.10.2 137 Cs dial value (NA) on Capintec ........................................................ 73 CHAPTER FIVE ..................................................................................... 75 CONCLUSION AND RECOMMENDATIONS ................................... 75 5.1 Conclusion ................................................................................................... 75 5.1.1 Recommendations ................................................................................ 75 5.1.2 Nuclear Medicine Department ............................................................. 76 5.1.3 Nuclear Regulatory Authority and Radiation Protection Institute ....... 76 5.1.4 Research Community ........................................................................... 76 REFERENCES ........................................................................................ 77 APPENDIX ............................................................................................. 81 viii University of Ghana http://ugspace.ug.edu.gh LIST OF FIGURES Figure 2.1: Schematic representation for charged particle interactions. .................... 10 Figure 2.2: The three major photon interactions with matter for different energies.11 Figure 2.3: Graph showing the variation of the pulse height with voltage Vdc . ...... 14 Figure 2.4: Schematic representation of a dose calibrator ........................................ 15 Figure 2.5: Radionuclide calibrator............................................................................ 16 Figure 2.6: Energy-response curve using Co-60 as standard source. ........................ 20 Figure 3.1: Some materials used for the study ........................................................... 35 Figure 3.2: FHG LAF shielded Radiochemistry Cappa/fume hood with Comecer dose calibrator. ........................................................................................ 37 Figure 3.3: Capintec CRC-15R dose calibrator ......................................................... 37 Figure 3.4: Vial containing 137Cs standard radionuclide source ................................ 38 Figure 3.5: Interface for Microsoft Excel 2010 ......................................................... 39 Figure 3.6: Interface for Minitab 16 software ............................................................ 40 Figure 4.1: (a) Graph of activity against number of weeks for constancy check (b) Relative deviation against number of weeks for constancy check on Comecer and Capintec dose calibrators. ................................................. 49 Figure 4.2: (a) Relative response test for Comecer and (b) Relative response test for Capintec using 137Cs standard radionuclide source. .............................. 50 Figure 4.3: (a) Measured 137Cs activity against number of weeks (b) Deviations of measured activity about the true activity of 137Cs standard radionuclide source. ..................................................................................................... 51 Figure 4.4: Decay curves for 99mTc activities on Capintec and Comecer dose calibrators. ............................................................................................... 54 ix University of Ghana http://ugspace.ug.edu.gh Figure 4.5: Linearity response for Capintec and Comecer dose calibrators on logarithmic scale. .................................................................................... 54 Figure 4.6: (a) % of 99mTc activity overestimated by Capintec over entire range of activities used and % of 99m(b) Tc activity overestimated by Capintec over useful clinical range. ....................................................................... 55 Figure 4.7: Drifts in Capintec electrometer readings ................................................. 56 Figure 4.8: Effects of residual contamination for Capintec ....................................... 57 Figure 4.9: Dipper and liner contamination levels for Capintec ................................ 58 Figure 4.10: Volume correction factor against sample volume for Comecer and Capintec dose calibrators using a 10ml vial. ........................................... 60 Figure 4.11: (a) Activity against source volume for vial (b) Error due to volume of source in vial. .......................................................................................... 60 Figure 4.12: VCF against sample volume for the 2ml syringe. ................................. 62 Figure 4.13: The influence of Source container and sample volume on assayed 99mTc activity within 2% and 5% uncertainties. ................................................ 63 Figure 4.14: Normalized 137Cs activity against number of reading within 5% error margin...................................................................................................... 65 Figure 4.15: Error due to 137Cs calibration factor. ..................................................... 66 Figure 4.16: Calibration curve for Capintec with Comecer as reference dose calibrator over entire range of 99mTc source activities used. ................... 67 Figure 4.17: Calibration curve for Capintec with Comecer as reference dose calibrator over useful clinical range of 99mTc source activities. .............. 68 Figure 4.18: Error due to old and New dial values for 99mTc assays on Capintec. .... 72 x University of Ghana http://ugspace.ug.edu.gh LIST OF TABLES Table 2.1: Specifications for two common radionuclide calibrators………………17 Table 2.2: Dose calibrator quality control tests ……………………………………25 Table 2.3: Limits of acceptability for different standards for dose calibrators ……30 Table 3.1: Specifications for Capintec CRC-15R and Comecer dose calibrators… 36 Table 4.1: Physical inspection…………………………………………………….. 46 Table 4.2: Daily tests on Capintec …………………………………………………47 Table 4.3: Daily tests on Comecer ………………………………………………....48 Table 4.4: Constancy check …………………………………… ………………....48 Table 4.5: Relative response of calibrators to 137Cs radionuclide source ……….....49 Table 4.6: Accuracy of Comecer and Capintec …………………………………....51 Table 4.7: Linearity response for Comecer to 99mTc radionuclide source…...…….52 Table 4.8: Linearity response for Capintec to 99mTc radionuclide source…..…..…53 Table 4.9: Geometry dependence for Comecer and Capintec dose calibrators …..59 Table 4.10: Further vial geometry test for Comecer and Capintec ……………….61 Table 4.11: Measurements accuracy with Comecer dose calibrator……………... 64 Table 4.12: Measurements accuracy with Capintec dose calibrator……………... 64 Table 4.13: Excel validation of 99mTc calibration ……….. ……………………....69 Table 4.14: Minitab validation of 99mTc calibration ………..………………….... 70 Table 4.15: Old and new dial value for 99mTc on Capintec ……………………....71 Table 4.16: Practical range of 99mTc dial value on Capintec ……………….…....72 Table 4.17: New dial value for 137Cs on Capintec………………………………. 73 Table 4.18: Practical range of 137Cs dial value …………………..………….…...74 xi University of Ghana http://ugspace.ug.edu.gh LIST OF ABBREVIATIONS AND SYMBOLS 99m Tc Technetium 99m Cs-137 Cesium 137 eV Electron volt GBq Gigabequerel KeV Kiloelectron volt mCi Millicurie MBq Megabequerel AAPM American Association of Physicists in Medicine ANSI American National Standards Institute IAEA International Atomic Energy Agency IEC International Electrotechnical Commission NCRP National Council on Radiation Protection and Measurements NIST National Institute of Standards and Technology NPL National Physical Laboratory QA Quality Assurance QC Quality Control xii University of Ghana http://ugspace.ug.edu.gh ABSTRACT Dose calibrators are used for accurate measurement of radionuclide activity which is required to achieve the desired efficacy for the best clinical outcome. Observations from assayed activity with Capintec and Comecer dose calibrators at the nuclear medicine department of the Korle-Bu Teaching Hospital have indicated that the two systems report significantly different (>10%) readings for the same activity source. Also unusually high background readings (>20% of the mean) have been noted at the 137Cs and 99mTc radionuclide settings for Capintec. The study therefore investigated the reasons for these observations so as to cross-calibrate the two systems to enable accurate measurements of radionuclide sources. Constancy check with 137Cs standard radionuclide source found Comecer and Capintec systems to have standard deviations of 1.2% and 0.74% respectively.The study also revealed deviations within ±5% tolerance for relative response to 137Cs standards at clinically significat radionuclide settings for both systems. The results for accuracy in the measurement of 137Cs standards for Comecer and Capintec systems were found to be 185.1 µCi ±1.4% and 193.7 µCi ±3.1% respectivey. Using constant activity method, both vial and syringe geometry testing yielded uncertainties within ±2% tolerance for both systems. Linearity response for both systems yielded deviations within ±5% tolerance. However, the study revealed underestimation with Comecer and overestimation with Capintec for 99mTc assays below 1 mCi by 13-16% and 11-31% respectively. The study also found evidence of residual contamination for Capintec systems within tolerance levels. A calibration curve was developed to determine theoretical activities of 99mTc on Capintec with Comecer as the reference dose calibrator and the results gave assay accuracy within ±5% tolerance levels. Investigation of the influence of xiii University of Ghana http://ugspace.ug.edu.gh dial values supplied by Capintec on the measured activity readings on their system found drifts in the gain settings to be the reason for higher measurement readings as compared to Comecer system. However, new dial values were theoretically determined and the gain setting was adjusted to give assay accuracy within ±5% tolerance for 99mTc and 137Cs sources. Performance evaluation and cross-calibration have been done on Capintec and Comecer dose calibrators. The study revealed variations in the performance of both systems within tolerance levels recommended by standard protocols using appropriate settings and procedures (AAPM Report 181, 2012, IAEA TRS 454, 2006, ANSI N42.13 2004, and IAEA-TECDOC-602, 1991). xiv University of Ghana http://ugspace.ug.edu.gh CHAPTER ONE INTRODUCTION 1.1 BACKGROUND Nuclear medicine is the branch of medical imaging that uses small amounts of radioactive materials for diagnosis, staging of disease, therapy and monitoring the response of a disease process (Bailey et al, 2014). The tracer principle is used in nuclear medicine because of its ability to utilize small amounts of radioactive substance in living organisms without significant pharmacological effect on the body. The practice of nuclear medicine involves administering small amounts of radio-labeled compounds called radiopharmaceuticals. The radiopharmaceutical administered to the patient orally, intravenously or by inhaling localizes in the target cell for either diagnostic or therapeutic purposes. Diagnostic radiopharmaceuticals yield information about where they are localized which can help imaging of the organ of interest in patient using special gamma cameras such single photon emission tomography (SPECT) or positron emission tomography (PET) imaging system. On the other hand, therapeutic compounds target specific tumors, such as thyroid, lymphomas or bone metastases, delivering radiation to tumorous lesions for the purpose of curing, destroying, mitigating or controlling the disease (Bailey et al, 2014 and Cherry et al, 2012). The activity of a radiopharmaceutical is accurately assayed with the use of a dose calibrator (radionuclide dose calibrator). The accuracy of measurements should be covered by consistent quality control of the instrument, including a daily constancy test, a quarterly linearity test, an annual accuracy check and periodic reassessment of its calibration, traceable to secondary standards (IAEA TRS 454, 2006). 1 University of Ghana http://ugspace.ug.edu.gh Tyler and Woods (2003) report that it is a good practice to re-measure syringe activity while taking into account geometry dependence so as to administer the correct activity to patients. To reduce the error due this geometry, volume correction factors have to be derived for several medically important radionuclides. Clinically, a lower than actual activity implies that, the patient will be given a higher than prescribed dosage activity being unnecessarily burdened with extra radiation. On the other hand, a higher dosage of administered activity will be inadequate, demanding repetition of the process which implies extra dose to the patient and occupationally exposed staff. Quality control is therefore critical if the dose calibrator is to be used effectively. A nuclear medicine facility should therefore ensure dose calibrators are regularly checked for any calibration errors to ensure that assay errors of prescribed dosage fall within recommended limits (Khan et al, 2016). The International Atomic Energy Agency (IAEA) recommends an assay accuracy of ±5% while the American National Standards Institute (ANSI) recommends ±10% assay accuracy for a radionuclide dose calibrator. In most countries, the limit is for a given dose to fall within ±10% of the prescribed dosage (IAEA TRS 454, 2006 and ANSI N42.13, 2004). 1.2 STATEMENT OF THE PROBLEM Accurate measurement of radionuclide activity is required to achieve the desired efficacy and for the best clinical outcome. Although some manufacturers of the dose calibrators claim high accuracy and reproducibility for the radioactivity measurements, yet few studies have reported variations in these parameters (Sharma et al, 2015). 2 University of Ghana http://ugspace.ug.edu.gh Bailey et al (2014) reports errors ranging from 64 to 144% of the expected activity using calibration factors supplied by manufacturers of radionuclide dose calibrators. This re-emphasized the need for consistent quality assurance programme to confirm calibrations within a Nuclear Medicine unit. Other researchers have reported differences in assayed activity for VDR-15R and CAPINTEC CRC®-25R calibrators within ± 10% tolerance as required by well- established international standards. To maintain the effective use and proper function of the dose calibrator, a further evaluation criterion was recommended to include a daily constancy check, an annual accuracy check and a quarterly linearity test (Assan et al, 2012 and IAEA TRS 454, 2006). The nuclear medicine department of the Korle-Bu Teaching Hospital has Capintec CRC®-15R and Comecer radionuclide dose calibrators. Observations from assayed activity have indicated that the two systems report significantly different (>10%) measurement readings for the same activity source. This study therefore seeks to investigate the reasons for these observations so as to cross calibrate the two systems to enable accurate measurements from any of them. The overall performance of the two systems will also be assessed and evaluated through accuracy, constancy, geometry and linearity quality control tests. 3 University of Ghana http://ugspace.ug.edu.gh 1.3 OBJECTIVES OF THE STUDY The principal objective of the study is to cross calibrate CAPINTEC ® CRC 15R and COMECER dose calibrators in use at the Nuclear Medicine Department of Korle-Bu Teaching Hospital. The specific objectives are: 1. To assess the performance of Capintec and Comecer dose calibrators. 2. To establish calibration factors for accurate measurement of radionuclide activity on the two systems. 3. To re-calculate dial values for some clinically significant and available radionuclides. 1.4 RELEVANCE AND JUSTIFICATION Dose calibrators are very important in the practice of nuclear medicine. Their proper use requires a comprehensive quality assurance program to assure the nuclear medicine practitioner that the doses of radioactive materials being administered to the patients are sufficient for the task and do not harm the patient. It is in light of this that the work undertaken in this thesis is important. It is an attempt to evaluate the performance of dose calibrators in the Nuclear Medicine Unit of Korle Bu Teaching Hospital, especially in the absence of a rigorous programme of maintenance and calibration of such equipment in the country. Results from the comprehensive quality control tests on Capintec and Comecer radionuclide dose calibrators will serve as an integral component of a quality assurance programme at the nuclear medicine department of the Hospital. The study will provide specifically derived calibration and volume correction factors which would be used for future reference by nuclear medicine personnel. The calibration 4 University of Ghana http://ugspace.ug.edu.gh curve/equation from cross calibration between the two systems will be available to help provide a means of ensuring the correct activity is administered to patients even in the case where one of the radionuclide dose calibrators develops a fault. The cross- calibration will in itself be a quality control measure and serve as double check on radionuclide activity to be administered. Finally, results and recommendations from the study will be valuable to the Nuclear Regulatory Authority for quality assurance audits and also serve as benchmark for further research. 1.5 SCOPE AND DELIMITATION The research was done at the nuclear medicine department of the Korle-Bu Teaching Hospital in Accra within the period September 2017 to July 2018. The study covers general QC tests (accuracy, constancy, linearity and geometry) performed on Capintec and Comecer dose calibrators. The research also investigated the influence of predetermined dial values on the assay accuracy of Capintec radionuclide dose calibrator. 1.6 ORGANISATION OF THESIS The thesis consists of a chronological order of five chapters. Chapter one describes the general background to the research, provides an overview of the existing state of knowledge relevant to the study and gives the organization of the thesis. The literature relevant to the research problem is reviewed in chapter two. Chapter three focuses on the materials and methodology of the study. The results obtained are presented and discussed in chapter four. Chapter five covers the conclusions and recommendations from the study. The references section contains citations of other researches and papers relevant to the study. An appendix section is also given for details on the data collected. 5 University of Ghana http://ugspace.ug.edu.gh CHAPTER TWO LITERATURE REVIEW 2.1 BASIC PHYSICS OF THE DOSE CALIBRATOR 2.1.1 Radioactive decay Radioactive decay is the process in which an unstable nucleus releases matter and/or energy during a transition to a more stable form. It may do so by releasing sub- atomic particles and energy, or by capturing an orbital electron into its nucleus thus releasing energy. Atoms that are unstable are also known as radioactive atoms, or radionuclides. The original, radioactive atom is known as the parent. The new nucleus (after decay) is known as the daughter radionuclide. The activity of a radioactive source is the number of disintegrations per second. The SI unit of activity or decay rate is the Becquerel (Bq). The Curie (Ci) is the traditional unit for radioactivity and it approximates the disintegration given out every second by 1g of radium in a state of equilibrium with daughter nuclei (Maher et al, 2006). 1Ci  3.71010 Bq 1Bq 1ds1 Although radioactivity is a random and spontaneous process each radionuclide decays at its rate, having its own decay constant (λ). dN   N (2.1.1) dt The negative sign shows that the number of nuclei N decreases as time elapses. The activity of a radioactive source A is given by the quantityN . 6 University of Ghana http://ugspace.ug.edu.gh The strength of a radioactive source is therefore given by its activity. The solution to first order equation (2.1.1) above is the following function: t N(t)  N0e (2.1.2) Where, N (t) is the number of nuclei present at time t and N0 is the initial number of nuclei at t0 respectively. From above, the activity can therefore be written as t A(t)  A0e (2.1.3) Where, A(t) is the activity at time t and A0 is the initial activity at t0 respectively. The process of decay is random for individual atoms. Although the exact moment of an individual atomic decay cannot be predicted, the probability of decay during a given time period can be measured (based on observations from a large number of atoms). The decay constant (λ) is expressed in units of probability per unit time (Cherry et al, 2012 and Maher et al, 2006). The half-life is the time required for 50% of the parent atoms to undergo radioactive decay. Substituting and N(t)  0.5N0 into (2.1.2) gives the relation between the half-life and decay constant ( ): (2.1.4) Where  is the mean lifetime, defined as the time taken for the nuclei to decay to 1 N . Also substituting (2.1.4) into (2.1.3) yields; e 0 ( ) ( ) ( ) (2.1.5) Where n is the number of half-lives. 7 University of Ghana http://ugspace.ug.edu.gh 2.2 INTERACTION OF RADIATION WITH MATTER Ionizing radiation can be classified into either particulate type (α particle, β particle, etc.), or non-particulate type, such as high-frequency electromagnetic radiation (e.g., γ rays, X-rays, etc.), and both kinds are ionizing radiations. As shown in Figure 2.1, the mechanism of interaction of the two types of radiations with matter is different and forms the basis on which activity is measured (Cherry et al, 2012 and Maher et al, 2006). 2.2.1 Charged particle interaction with matter Alpha-particle radiation (α-particle): Alpha radiation is identical to a helium nucleus ( 42 He ). The α-particle is positively charged (+2e) heavy nucleus, with short range in air, has low penetration and mostly emitted by a radionuclide with energy less than 10MeV. The low penetration makes the α-particle hard to detect. All α- decays go with the emission of photon radiation as the daughter nucleus de-excites. It is this emitted photon that makes it possible to measure activity of a nuclide (Cherry et al, 2012). β+ Radiation ((positron):β+ particle originates from the nucleus of an atom when a nucleus has too few neutrons relative to protons. A proton is converted into a neutron while releasing a β+ particle is emitted along with some energy. it loses its kinetic energy mainly through direct-ionization and then annihilates with its anti-particle (electron) to produce two 511keV photons in opposite directions (almost at 1800 with 8 University of Ghana http://ugspace.ug.edu.gh each other). These photons associated with β+ decay makes it easy to detect β+ radiation .β+ decay is also associated with de-excitation photons (Powsner et al, 2013 and Cherry et al, 2012). β- Radiation: a β-particle is a fast moving electron. This electron is ejected from the nucleus and mainly loses its kinetic energy by direct ionization. The range of most emitted β's is short. It should be noted that in β+ and β-emission, the emitted electron or positron has a continuous energy spectrum, which ranges from the maximum transition energy Emax to zero. β-radiation (except a few high energy βs) is easily stopped in a material. As shown in Figure 2.1, the electron loses energy and continuous low energy photons are emitted. The emission is referred to as Bremsstrahlung. Many radionuclides that decay by β emission also emit de- excitation photons (x-rays, γ-rays), which can be detected to measure the activity of a sample (Powsner et al, 2013 and Cherry et al, 2012). 9 University of Ghana http://ugspace.ug.edu.gh Figure 2.1: Schematic representation for charged particle interactions. Source: Physics in Nuclear Medicine by Cherry et al, 2012, p.64 E-Book: Elsevier Health Sciences. A represents Photon interaction with an outer electron resulting into ionization and B, Interaction with a nucleus, resulting in bremsstrahlung production (Cherry et al, 2012). 2.2.2 Interactions of Photons with Matter The energy of a photon is the major determinant of the mechanism by which it interacts with matter. The three main modes by which photons interact with matter to deposit their energy are discussed and illustrated in Figure 2.2 below. The boundaries show the values of Z and photon energy for which the effects are just equal. 10 University of Ghana http://ugspace.ug.edu.gh Figure 2.2: The three major photon interactions with matter for different energies. Source: Physics in Nuclear Medicine by Cherry et al, 2012, p.81 E-Book: Elsevier Health Sciences. Photoelectric Effect: In photoelectric effect an incoming photon interacts with and an electron which is bound to the atom. During this process, the photon is absorbed by the atom and an electron is ejected. The kinetic energy with which the photo- electron is ejected is equal to the difference between the energy of the incoming photon energy and the binding energy of the electron. In nuclear medicine, the photon energies of interest are between 30 and 300kev. This is due to the fact that, at these energies the electrons are more penetrating and thus able to participate in the photoelectric process. The photoelectric effect is therefore pre-dominant at low energies (interactions vary inversely as the third power of the energy). However, as photon energies become greater than the electron binding energies, the probability of the photoelectric process diminishes. At a certain energy, the number of photoelectric interactions per unit mass varies as the fourth power of the atomic number and is 11 University of Ghana http://ugspace.ug.edu.gh inversely proportional to the atomic weight of the medium (Z4/E3A) (Powsner et al, 2013 and Cherry et al, 2012). Compton Effect: The Compton Effect is the interaction of a photon with a free electron. If the energy of the incoming photon is much greater than the binding energy of the electron, the electron is said to be a free (unbound). The kinetic energy of the electron that is scattered is dependent upon the angle through which it is scattered. In order to impart all its energy to the medium, the scattered photon must continue to interact with the medium. Compton Effect is pre-dominant for high photon energies (ranging from 100 keV to 10 MeV) for atomic numbers for detector materials. At 100 keV, the maximum kinetic energy of the scattered electron is about 30 % of the incoming photon; at 1 MeV, it is about 80 %; and at 10 MeV, about 98%. The number of Compton interactions per unit mass is approximately proportional with the energy the incoming photon and atomic number but inversely proportional to the atomic weight of the medium (ZE/A) (Cherry et al, 2012). Pair Production: In the presence of the nuclear field, the incoming photon disappears and an electron-positron pair is produced. This process is called pair production. In order to produce an electron-positron pair, the incoming photon energy must be at least greater than 1.022 MeV (twice the mass of an electron). Pair production is pre-dominant at very high energies, that is, above about 10 MeV. The number of pair production interactions per unit mass is proportional to the square of the atomic number and inversely proportional to the atomic weight of the medium (Z2E/A) (Powsner et al, 2013 and Cherry et al, 2012). 12 University of Ghana http://ugspace.ug.edu.gh 2.2.3 Gas filled detectors As already seen above, the creation of ions is one of the results from the interaction of radiation with matter. This outcome is utilized by gas-filled detectors. In gas-filled detectors, the atoms of a gas are ionized by the radiation. Thus, the detector is the gas and can be used to measure radiation fields if the relationship between the radiation field and the charge produced is known. The radiation enters the detector and interacts with the gas or with the walls of the chamber. It must be pointed out that photons cannot produce ionization directly, but must first interact with the chamber material (gas and wall) to produce electrons (Maher et al, 2006). That is, through a series of interactions, the photon transfers its energy to one or more electrons. The electron is slowed down through collisions with the chamber gas (argon). The collisions knock electrons off the molecules producing positive ions (this is the ionization process). An electric field is set up by the collection voltage across the chamber as positive ions drift towards the cathode and the electron drifts towards the anode, thus producing a current. The electronic circuitry then measures either the current or the total charge produced during the period of interest (Bailey et al, 2014 and Maher et al, 2006). A gas-filled detector is commonly cylindrically shaped, with a well-insulated outer wall from a central electrode. Depending on the design of the detector and the voltage Vdc applied across the electrodes, its operation can fall in any of three regions (i.e. the ionization region B, proportional region C or Geiger–Müller (GM) region D) shown in Figure 2.3 below (Maher et al, 2006). 13 University of Ghana http://ugspace.ug.edu.gh Figure 2.3: Graph showing the variation of the pulse height with voltage Vdc . Source: Basic Physics of Nuclear Medicine by Maher et al, 2006, p.58. Libronomia Company: Wikibooks. As be seen in Figure 2.3, the graph is divided into five main regions; Region A: Here Vdc is very low and recombination of the electrons and positive ions takes place. Consequently, the pulse height is small due to the insufficient collection of ion pairs. As the applied voltage increases, recombination diminishes (Maher et al, 2006). Region B: Vdc is appreciably high in this region so recombination is almost negligible. This region is called the ionization region and this is the operation region for a type of gas filled detector called ionization chamber. This is the region in which dose calibrators operate. Region C: Vdc is sufficiently great to cause the electrons approaching the central wire to gain sufficient energy for collisions with the gas atom electrons to produce more ion pairs. Consequently, the number of electrons is increased so that the charge through the resistor may be very high (i.e. in the orders of thousand times) compared 14 University of Ghana http://ugspace.ug.edu.gh to the charge produced primarily by the radiation interaction. A detector known as proportional counter operates in this region (Maher et al, 2006 and Podgorsak, 2005). Region D: Vdc is so huge that even a weakly-ionizing particle creates a large voltage pulse. The primary ionization brought about by the radiation causes a complete gas breakdown as an avalanche of electrons drift towards and spreads along the central wire. This region is referred to as the Geiger-Müller Region and the detector that utilizes this it is called Geiger counter. Region E: This region cannot be used for the detection of radiation events since any further rise in Vdc is sufficient enough to completely cause gas breakdown (Maher et al, 2006). 2.2.4 The modern radionuclide calibrator Figure 2.4: Schematic representation of a dose calibrator 15 University of Ghana http://ugspace.ug.edu.gh The calibrated re-entrant ionization chamber is commonly referred to as a dose calibrator. The instrument is able of provide accurate radioactivity measurements within clinically acceptable levels when properly calibrated, operated, and serviced. The chamber is typically made of aluminum enclosed with argon under pressure (1-2 MPa or 10-20 atm). It has a perspex well lining material easily removable for cleaning to prevent the chamber from accidental contamination. A vial holder (dipper) into which a syringe or vial is placed is provided to maintain the source geometry and ensure optimal positioning within the chamber. The chamber is normally pre-shielded with 6mm of lead by the manufacturer in order to lower the influence of background radiation IAEA-TECDOC (1991). Figure 2.5: Radionuclide calibrator Source: Essentials of Nuclear Medicine Physics and Instrumentation by Powsner et al, 2013, p.48. John Wiley & Sons. 16 University of Ghana http://ugspace.ug.edu.gh Table 2.1 shows some specifications for two common radionuclide dose calibrators. Table 2.1: Specifications for two common radionuclide calibrators Specification Capintec CRC-25R Atomiclab 200 Ionization chamber 26cm deep×6cm diameter 26.7cmdeep×7cm diameter dimensions Measurement range Auto ranging from Auto ranging from 0.001MBq 0.001MBq to 250GBq to 399.9GBq Nuclide selection 8 pre-set, 5 user-defined 10 pre-set, 3 user-defined (80radionuclide (94radionuclide calibrations in calibrations in memory) manual) Display units Bq or Ci Bq or Ci Electrometer accuracy <±2% <±1% Response time Within 2s 1s for activities >75MBq Repeatability ±1% ±0.3% Source: Nuclear Medicine Physics: a Handbook for Teachers and Students by Bailey et al 2014, p.252. Vienna: International Atomic Energy Agency (IAEA). 2.2.1 Absorbed dose via measurement of current or activity People or biological systems exposed to radiation are at potential risk of radiation dose being delivered. The quantity of energy deposited per unit mass is the absorbed dose. It is therefore important to distinguish between the activity of a radioactive source and the radiation dose which may result from the source. The radiation dose depends on the location of the source with regard to those exposed. Furthermore, the radiation dose depends upon the type of radiation, such as whether it is α, β or γ-rays and the energy of the radiation. The energy is transferred in small quantities for each interaction between the radiation and a molecule and there are usually many such interactions. Radiation results in the formation of positive and negative ions in a gas as well as in all other materials (Bailey et al, 2014). 17 University of Ghana http://ugspace.ug.edu.gh When a syringe or vial enclosing the radioactive sample is placed into the source holder and gently lowered into the chamber, the inactive gas is ionized; ion pairs drift towards opposite polarity thus setting up an electrical current. This current between the electrodes is proportional to the activity of the assayed radioisotope. The magnitude of this current is usually small (on the microampere level) even if higher activity is used. It is for this reason that an electrometer is coupled to the dose calibrator in order to quantify this minimal electric current and convert the display into activity in MBq or mCi (Bailey et al, 2014 and Powsner, 2013). 2.3 CALIBRATION OF DOSE CALIBRATORS Calibration involves the determination of a numerical relationship, with its associated uncertainty, between an observed measurement and its expected value using a standard system, based on reference sources, traceable to national primary standards of radioactivity. Traceability is the characteristic of a result or value of a standard by which it can be linked to some references, normally national or international standards, through a continuous chain of assessments, all having defined uncertainties (Gagnon et al, 2010 and Gadd et al, 2006). Calibration of dose calibrators may also involve determining dial settings for each radioisotope to be assayed. Manufacturer calibration settings are given as dial settings (calibration factors) for individual radionuclides. However, these settings may vary slightly because the chamber response depends on the type of radionuclide, its geometry (source vessel type and volume) and height in the chamber. Therefore, in order to ensure accurate measurement for each radionuclide, the assay must be made using the appropriate calibration setting and correct geometry for which the system was calibrated (AAPM Report 181, 2012 and Gadd et al, 2006). 18 University of Ghana http://ugspace.ug.edu.gh Sharma et al (2015) reported a cumulative error of about 20.0% with respect to the accuracy in the measurement of radioactivity for the beta‑gamma emitters. There is consequently the need to redefine the manufacturers’ quoted values of the calibration settings of the dose calibrators used in a given hospital‑based clinical setting. Although most dose calibrator are purchased pre-calibrated by the producer for frequently used radioisotopes, the dial values need periodical review as they are originally determined through measurements of primary or traceable standard sources for a master system before they are transferred to a production system as calibration settings. The settings can also be calculated using energy-response curves obtained using available decay schemes. It is recommended for medical facilities, radiopharmaceutical companies or commercial nuclear pharmacies to occasionally review and verify if these calibration settings are traceable to NIST standards (AAPM Report 181, 2012). Tyler and Woods (2003) report significant differences between the dial values for syringes and glass vials due to different energy photon emissions from the decay of the radionuclides; the lower the energy, the greater the difference. Large differences were observed for 125I and only small differences for 131I. However, for radionuclides such as 99mTc and 67Ga, variations of up to 30% have been observed indicating the importance of specifically derived calibration factors as well as emphasizing the complexity of the problem with regard to geometry influence. 2.3.1 Energy-response Curves (Photons) Calibration settings for the chamber can be determined for individual radionuclides. The energy efficiency N , of the ionization chamber for a radioactive source is given 19 University of Ghana http://ugspace.ug.edu.gh by the reciprocal of the calibration setting and can be written as the summation of two components:  N Pi Ei  i Ei  (2.3.1) i Where Pi Ei  is the emission probability for each disintegration of photons with energy Ei and  i Ei  is the efficiency of the chamber. A number of calibration coefficients are obtained using well known reference sources within required energy window. The chamber’s response as a result of particular photons from the radioisotope is then determined, standardized to a reference source, and plotted to obtain the energy- response profile. Figure 2.6 below shows a characteristic curve using 60Co as standard source for an aluminum alloy wall ionization chamber for a commercial radionuclide dose calibrator (Bailey et al, 2014 and AAPM Report 181, 2012). Figure 2.6: Energy-response curve using 60Co as standard source. Source: AAPM Report TG 181, 2012, p.10. 20 University of Ghana http://ugspace.ug.edu.gh For aluminum-walled chambers, photons with energies around 13 keV are blocked from reaching the sensitive volume of the chamber. The actual threshold varies depending upon the source container wall material, its volume and thickness. The thickness differs from system to system due to manufacturing discrepancies. As seen in Figure 2.6, from a low-energy cut-off, ionization current rises sharply and then falls suddenly, producing a peak at roughly 50 keV. The peak is as a result of the opposing effects that a rise from photon transmission through the source, container and chamber wall (since photoelectric effect falls sharply), together with the subsequent reduction in photon interaction with the chamber volume. Compton scatter dominates at almost 50 keV. Above 200 keV Compton scatter is predominant and the response rises with increase in photon energy. Thus, efficiency is minimal at low energies, has a peak around 50 keV, drops to a minimum at 200 keV, before increasing proportionally to energy (Bailey et al, 2014 and AAPM Report 181, 2012). 2.3.2 Dial value or Calibration number (NA) The dial value or calibration number ( ) is the factor dialed into the calibrator to give the desired gain. A calibration number helps to convert the measured current to a nominal activity. This means that a dose calibrator requires a different dial value for each individual radioisotope to be measured (Prekeges, 2012). The size of a calibration factor is also determined by the chamber (thickness of inner wall, pressure of the gas, design, and applied voltage), geometry of source (vessel type, thickness, its volume) and location of the sample in the chamber (Prekeges, 2012 and Capintec 2007). 21 University of Ghana http://ugspace.ug.edu.gh 2.3.3 Determining dial values for Capintec dose calibrator (Capintec 2007, 2015). It is very convenient to express the response of the detector to a radioisotope, N, relative to that of a standard reference material (SRM), e.g. Co-60. ( ) ( ) ( ) The sensitivity of the detector for a photon of energy is defined as: ( ) The detector response and the sensitivity have the following relation: ∑ ( ) Where is the intensity of the photon whose energy is . The relationship between the response of the detector and the gain setting (relative to that for 60Co, in order for the instrument to give a direct reading of the activity) is given by: ( ) Capintec calibrators are calibrated with certified Cobalt-60 and Cobalt-57 standard radionuclide sources. The calibration setting number of Capintec Calibrators for a radioisotope A, is given by ( ( ) ) ( ) ( ) Where: 22 University of Ghana http://ugspace.ug.edu.gh NCo-60 and NCo-57, and RCo-60 and RCo-57 are the calibration numbers and responses for 60Co and 60Co standard radionuclide sources respectively. For Capintec these are assigned the following numbers: NCo-60 = 990, NCo-57 =112 , Substituting the values for NCo-60 and NCo-57, and RCo-60 and RCo-57 into equation (2.3.6) equation (2.3.7) below is obtained: ( ) ( ) However, as seen in equation (2.3.5) the gain is inversely proportional to the response , we can therefore rewrite (2.3.7) as: ( ) The accuracy of the sensitivity curve and calibration number determined are tested by calculating calibration numbers for all radioisotope standards used for the studies of the sensitivity. The agreement between the calculated and observed responses should be within ±3% tolerance (Capintec 2007, 2015). 23 University of Ghana http://ugspace.ug.edu.gh 2.4 DOSE CALIBRATOR QUALITY CONTROL TESTS 2.4.1 Quality Assurance and Quality Control For dose calibrators quality Assurance (QA) is a systematic tool for checking and evaluating the attainment of high standards of efficiency and reliability in the practice. It encompasses management plans to guarantee the dependability of the production system. QA helps in minimizing the uncertainties and errors in equipment performance. Quality Control (QC) refers to the specific measures put into place to ensure that each particular aspect of the procedure is reliable (IEC TR 61948-4, 2006 and IAEA-TECDOC, 1991). Specifically, QC is part of the QA programme and is essential for the submission of requirements for procedures; the preparation and administration of radiopharmaceuticals. QC is essential for radiation protection of patients, staff and the general public. It also serves as an important component in the preparation of patients; the setting-up, use and repairs of electronic devices; the method of the actual procedures; the investigation and interpretation of images; the reporting of results and, finally, for record keeping . A radionuclide dose calibrator must therefore be covered by a comprehensive QA programme. It is important to carry out the test procedures correctly since the safety of the patient is highly reliant on the accuracy of measurements from the radionuclide dose calibrator. Often, procedural errors in performing QC on calibrators seem to be unavoidable even by experienced users. It is therefore important to adhere to guidelines given in the user manual. The QC tests performed on dose calibrators are shown in Table 2.2 (IAEA TRS 454, 2006 and IAEA-TECDOC, 1991). 24 University of Ghana http://ugspace.ug.edu.gh Table 2.2: Dose calibrator quality control tests QC test Frequency Source Half-life Energy (keV) Constancy Daily 137Cs 30 years 662 Check Linearity Installation, quarterly, response After repairs and 99mTc 6hours 140 test when displaced to new location. Accuracy Installation, annually 60Co 5.3years 1170, 1330 test and after repairs. 137Cs 30 years 662 133 10.51 years 356 Ba 57 271.7 days 122 Co Geometry Installation and after 99m 6 hours 140 test repairs. Tc 2.4.2 Constancy check Constancy means reproducing a measurement result whenever the same source is assayed over a period of time, taking into account its decay. Constancy test measures the dose calibrator’s ability to give reproducible readings daily on all available radioisotope windows likely to be encountered. This test should be performed daily using a long-lived source, usually 137Cs. It is strongly recommended that the same source be readily available for use throughout the life of the calibrator. Variations in displayed activities must fall within ± 5% of the most recent reading at that setting with background and decay considered (de Farias Fragoso, 2013 and IAEA- TECDOC, 1999). 25 University of Ghana http://ugspace.ug.edu.gh 2.4.3 Linearity of response test Linearity testing measures the ability of the calibrator to give the correct reading over the entire range of activities of its usage. The test is performed at installation and quarterly and using a syringe or vial of 99mTc with activity as high as the maximum normally prepared in radiopharmaceutical kit, in a unit dosage syringe administered to a patient, or in therapy, whichever is largest. In a Mo-99/Tc-99m generator this activity may be the total eluate in a radiopharmaceutical kit. It is recommended to carry out the test at installation, quarterly, after repairs and if there is displacement to new location (Ahmed, 2015 and Mo et al, 2006). Linearity test can be performed using a number of methods (i.e. decay, shielding and proportional methods). The decay method involves assaying a high activity of a short-lived radionuclide, normally 99mTc source at an initial time T0 and at pre- determined intervals of time until activity falls below 30 μCi. The expected and measured activities are compared to ascertain the instrument’s linearity over the entire range of activities. This test also reveals the region and extent of non-linearity arising from saturation effects (ion-recombination); non-linearity near to zero activity (may indicate a wrong preset zero adjustment) and discontinuities at change of range (systematic error in one of the ranges). The activity measured should be within ± 5% of its predicted value if the instrument is working properly (IAEA TRS 454, 2006 and IAEA-TECDOC, 1991). For the first calibration or reinstallation, the decay method is suitable for determining calibration factors to be subsequently used for the shielding method. There are several manufacturers of sets of lead lining that may be used for performing the linearity test using the shield method. The kit might have tubes of different colors representing different thicknesses of lead-lining. It may also have numbered and 26 University of Ghana http://ugspace.ug.edu.gh lettered cylinders of different thicknesses and different linings that are used in combination, each having different amounts of shielding to mimic intervals of 99mTc decay. These sets are calibrated when first acquired by ordering a 100 mCi 99mTc source and performing the linearity by the decay method as well as by the shield method. At the beginning of the decay calibration, measurements are also made with the tubes. The decayed measurements are used to verify that the calibrator had a linear response at the time of the cylinder calibrations for period of about 72 hours (Ahmed, 2015 and Capintec 2004). If the calibrator passes that test, then the tube attenuation measurements can be used as a calibration for all future linearity tests. A 100 mCi source is acquired and measured inside each of the tubes. The measured activity of each tube relative to no tube should be the same as the calibrated ratios. This then confirms maintenance of a linear response and is completed in just a few minutes. The proportional method of determining the linearity response can be confirmed by measuring the activity of a sample and then checking the activity of carefully weighed portions of the sample. The minimum activity of the initial sample should be as large as the highest activity normally measured. The ratio of the measured activities should be the same as the ratio of the measured weights or volumes (i.e. within ±0.5% uncertainty). The weights or volumes must be measured to a degree of accuracy much greater than the expected linearity (Capintec, 2007 and IAEA- TECDOC, 1991). 27 University of Ghana http://ugspace.ug.edu.gh 2.4.4 Accuracy test Accuracy is a measure of how close an observation is to the true value. It means that for given standard reference source, the indicated activity corresponds to the reading determined by NIST or the provider who has compared that source to one calibrated by the NIST. For a radionuclide calibrator, accuracy test is intended to indicate whether the calibrator gives correct readings over the entire energy scale (low, medium, and high) likely to be encountered from energy standards. Long-lived radionuclide sources, such as 137Cs (Energy = 662 keV) and 57Co (Energy = 122 keV), are repeatedly assayed in the calibrator and the mean of the measurements are compared with the decay-corrected values within stated tolerances issued by NIST for that particular reference source. If the readings differ significantly (>10%) from the standards then the calibrator should not be used. The test should be done at installation, annually, and after repairs or when the instrument is moved to a new location within the medical facility (Powsner et al, 2013 and IAEA TRS 454, 2006). Zeinali et al (2008) reported eight Nuclear Medicine centres in unacceptable situations with regards to dose calibrator assay accuracy. The study found two centres within 70% uncertainty, four over 30%, one had 28%, and the other one had 16% in terms of deviations in the measurement of the calibrated radionuclide standards. 2.4.5 Geometry test The geometry test is intended to show that accurate measurements can be obtained independent of the sample geometry or size. This test is done using a syringe that is normally used for injection. If volumes of syringes and vials differ from the recommended, they must be tested throughout the range of volumes commonly used. The test is performed at installation and after repairs. Volume correction factor 28 University of Ghana http://ugspace.ug.edu.gh (VCF) can be applied if the geometry test is within ±5% or else the calibrator must not be used (Powsner et al, 2013, Assan et al, 2012 and IAEA TRS 454, 2006). 2.4.6 Standards relating to dose calibrators The International Electrotechnical Commission (IEC, 1992; 1994) and a Technical Report (IEC/TR 61948-4, 2006) are two standards that apply to dose calibrators. IEC standards are often adopted by national standards organizations. Most manufacturers use IEC (1992) guidelines to ensure proper equipment functioning in a standardized way, while IEC (1994) is intended for operators of dose calibrators. On the other hand, the American National Standards Institute publication ANSI N42.13 (2004) is also often referenced by US manufacturers. ANSI states the least requirements of accuracy and repeatability for dose calibrators. The recommended assay accuracy of a reference source (activity above 3.7MBq) in a calibrator must be within ±10% of the stated activity with decay correction. The reproducibility must be within ±5% of the mean reading for that source from a series of ten consecutive measurements with activity larger than 100μCi (3.7MBq) in the same geometry. See Table below for some limits for of acceptability for some standards for dose calibrators. Table 2.3 shows some of the limits of acceptability for dose calibrators (Bailey et al, 2014, IEC TR 61948-4, 2006 and ANSI N42.13, 2004). 29 University of Ghana http://ugspace.ug.edu.gh Table 2.3: Limits of acceptability for different standards for dose calibrators Background Reproducibility Relative Accuracy Linearity Geometry (stability) response ANSI ±5% ±5% ±10% ±5% ---- IAEA ±20% ±5% ±5% ±5% ±10% ±5% ±2% NCRP ±5% ±5% ±5% ±5% AAPM ±5% ±5% ±5% ±5% ---- 2.5 SOME SOURCES OF ASSAY ERRORS 2.5.1 User errors Most dose calibrator systems are user friendly if properly set up and operated as directed in the manufacturer’s user guide. It is important for users to understand the calibrator’s functionalities and characteristics. It is the duty of the licensee to ensure proper training is given to individuals who use the calibrator. QC tests are to be done as required by the manufacturer and suitable action taken if errors are outside recommended limits. Users of dose calibrator must understand that calibration numbers are unique for each radionuclide and are specific to the geometry of source. Therefore, dippers must be used as indicated by the manufacturer and should be correctly positioned in the chamber, without physical alteration or damage. Dippers from different companies should not be exchanged without considering the influence on the accuracy of the calibration coefficients (AAPM Report 181, 2012). 30 University of Ghana http://ugspace.ug.edu.gh 2.5.2 Calibration geometry Ideally, manufacturers of dose calibrators calibrate their systems based on the type of radioisotope and the sample geometry used practically. However, this may not always be the case since calibrations must be derived for each container type and specific source geometry. Therefore, calibration settings derived by the manufacturer can be a source of assay error since they are prone to minor fluctuations in position and source configurations. This means that, any variation in these parameters may have a bearing on the accuracy of the measurement. It is up to the operator to verify whether the change is insignificant (<5%) or, if significant (>10%), new dial values need to be determined (AAPM Report 181, 2012 and Baker et al, 2005). Baker et al (2005) have observed significant deviations in terms of assay accuracy for 99mTc isotope. The accuracy in a number of cases was better than 5%. Precisely, 2% of the assays fell within 2% of the expected activity, 96% were within 5%, and only one assay was more than 10%. In this case the manufacturer’s assigned dial values were used. Nevertheless, the study did not reveal errors due to using geometry since measurements were done in the same geometry as calibrated. 2.5.3 Effects of an external shield The external shielding of the radionuclide calibrator provided by millimeters of lead has several advantages. It helps in the reduction of the background effects on the activity measurements, reduces radiation exposure to the personnel handling the radioisotopes and prevents efficiency changes caused by scattering material in the vicinity. The manufacturer normally shields the chamber with 6 mm of lead to minimize external influence on the system background (Gadd et al, 2006). 31 University of Ghana http://ugspace.ug.edu.gh However, the back scattering of photons and the emission of Pb K shell X-rays as a result of interactions within the lead shielding will modify the calibration factors. If extra shielding is needed, then the calibrator must be re-calibrated or correction factors should be determined to ensure correct readings are obtained. It is also worth noting that a shield positioned around or near a calibrator improves the sensitivity of the ionization chamber due to backscattering of photons by the shielding. For a Capintec calibrator the backscattering effects are more significant for photons of energies between 70 keV and 250 keV than photons in other energy regions (Capintec 2007). 2.5.4 Effects of container material Radioactive standard materials in the containers now being provided by NIST give a fair estimate of the assay of a radionuclide in a plastic or glass syringe ( wall thickness of 1.2 mm), even for radioisotopes with abundant low-energy photons. The operator should select, whenever possible, a standardized method, volume, and vessel for assaying radionuclides. The plastic syringe is suitable since it represents the delivery vehicle to the patient in most clinical conditions. Significant errors will occur in some instances, e.g., if the radioisotope is assayed in an appreciably different material and/or wall thickness than that of the standards. The vessels of most available standards from NIST are uniform. Plastic syringes also have a rather uniform wall thickness with low absorption (Capintec, 2007). 32 University of Ghana http://ugspace.ug.edu.gh 2.5.5 Effects of impurities The presence of radioisotope impurities affects the reading of the radionuclide dose calibrator, particularly in measurements of short-lived radionuclides several half- lives after initial preparation (unless this effect is removed by photon filtration as with 99Mo breakthrough in 99mTc). An ionization chamber itself does not have intrinsic energy- discrimination ability. The existence of radioisotope impurities will affect the reading of the calibrator unless the effect of impurities is eliminated by photon filtration as is done with 99Mo breakthrough in 99mTc. However, the presence of low-level radionuclide impurity does not negate the effectiveness of a dose calibrator, if the operator is aware of its presence and has an independently determined calibration including photons due to the impurities (Capintec, 2007). 2.5.6 Drift in the electronics of the calibrator The accuracy of the electrometer is another source of uncertainty over which the user may have little control. The electrometers’ inherent accuracy depends on the ability of the supplier to adjust the gain of the electrometer so that its measurement of current is traceable to primary standards. The adjustment is normally achieved by measuring the response of the system to a long-lived standard reference source and adjusting the electrometer gain until it indicates the true activity within the manufacturing tolerance. The gain of the system, however, will change with time and environment. This results from normal ageing effects of electrical components, such as resistors and capacitors, as well as the temperature, humidity and radiation exposure dependence of these components. If a reference source is supplied with the chamber, this allows the user of the facility to produce a benchmark reading when it is first supplied and to then adjust the electrometer gain if it changes with time (Gadd et al, 2006). 33 University of Ghana http://ugspace.ug.edu.gh The electrometer linearity is another source of uncertainty. The response is regarded as linear if the ratio of the measured response to the true response remains constant over the range of current inputs for which the calibrator is designed. Electrometers are expected to measure currents within a deviation from provided this is contained within reasonable limits; it may not be a significant problem (Gadd et al, 2006). 34 University of Ghana http://ugspace.ug.edu.gh CHAPTER THREE MATERIALS AND METHODS 3.1 Introduction This chapter presents the materials used to accomplish the study and the methods involved in arriving at the results. The materials include equipment and software used for the study. The study is an experimental study carried out at Korle-Bu Teaching Hospital in Accra-Ghana. The QC tests in this work were conducted in accordance with well-established and accepted international standards for dose calibrators (AAPM Report 181, 2012, IAEA TRS 454, 2006 and IAEA-TECDOC 602, 1991). 3.2 MATERIALS USED FOR THIS RESEARCH syringes Forceps/tongs gloves Source holder/dipper Vial shields Figure 3.1: Some materials used for the study 35 University of Ghana http://ugspace.ug.edu.gh Others: Non-radioactive saline solution and 773 mCi (28.6 GBq) of 99mTc activity 3.2.1 Materials and equipment Table 3.1 shows specifications for Capintec CRC®-15R and Comecer FHG LAF 40C1F dose calibrators were used in this study. Table 3.1: Specifications for Capintec CRC-15R and Comecer dose calibrators Specification Capintec CRC-15R Comecer FHG LAF 40C1F Chamber dimensions 2 5 . 4 c m d e e p × 6 . 1 cm diameter 28 cm deep×7 cm diameter Weight 13.6 kg 4 kg Resolution 0.001 MBq 0.15 MBq Measurement range Auto ranging from 0.001MBq Auto ranging from to 250 GBq 0.15MBq to 185 GBq Nuclide selection 9 pre-set, 4 user-defined 28 pre-set, user-defined radionuclide keys radionuclides keys Unit of display Bq or Ci Bq or Ci Electrometer accuracy Better than ±2% Better than ±2% Response time Within 4s-16s 1s -10s Repeatability ±1% ±1.5% 3.2.2 Comecer Dose Calibrator One of the most prominent manufacturers of dose calibrators for use in nuclear medicine units is Comecer. The fully digitized detector systems in Comecer models give quick and dependable read-out. This enables flexible integration of this detector into other systems or facilities, without the need of a converter or separate read-out. Comecer also has unit-measurement range of up to 2 Ci for 18F used in PET systems. 36 University of Ghana http://ugspace.ug.edu.gh Figure 3.2 below shows Comecer FHG LAF 40C1F calibrator in a radiochemistry fume hood system at Korle-Bu Teaching Hospital. Comecer display well chamber Figure 3.2: FHG LAF shielded Radiochemistry Cappa/fume hood with Comecer dose calibrator. 3.2.3 Capintec Dose Calibrator well Chamber Electrometer Figure 3.3: Capintec CRC-15R dose calibrator Capintec CRC-15R dose calibrator RAMSEY, N.J 07446 made in U.S.A. P/N 7120- 2204 manufactured in 1999 by Capintec was used in this study (see Figure 3.3). It is 37 University of Ghana http://ugspace.ug.edu.gh one of the most known dose calibrators because of its speed, simplicity and accuracy. This system takes advantage of the latest technology of auto-ranging for varying sample activity, giving it added speed, accuracy, and easy to use features. 3.2.4 Standard radionuclide source A long-lived 137Cs standard radionuclide sealed source in vial form (Code no. CDR562) of activity 9.21 MBq (248.92 µCi) calibrated for 13th October, 2005 and manufactured by AEA Technology QSA GmbH was used for constancy, relative response and accuracy tests. 137Cs Vial Figure 3.4: Vial containing 137Cs standard radionuclide source 3.3 SOFTWARE 3.3.1 Microsoft Excel 2010 The data collected was analyzed using Microsoft office 2010-Excel Program under windows 10. Microsoft Excel is a general spreadsheet software program for sorting, compiling and highlighting huge quantities of data. With new features such as spark 38 University of Ghana http://ugspace.ug.edu.gh lines and slicers, and improvements to Pivot Tables and other existing features, this version makes it easy to discover patterns or trends in the data. Finally, the multi-threading feature in Microsoft Excel 2010 helps speed up data retrieval, sorting, and other performance enhancements. These and many other features made the software suitable for use in data analysis for this study. Figure 3.5: Interface for Microsoft Excel 2010 3.3.2 Minitab 16 software Minitab is statistical software package used for all-purpose instructional application with easy interactive tools. Minitab was used due to its well suited capability to model systems making it a powerful primary tool for analyzing research data. 39 University of Ghana http://ugspace.ug.edu.gh Figure 3.6: Interface for Minitab 16 software 3.4 Methods 3.4.1 Physical inspection This involved inspecting both radionuclide calibrators’ general condition. The housing and particularly surroundings of the ionization chamber were examined for damage. Then compatibility of power supply requirements, controls, plug-in modules, push-buttons and switches were also checked. Other connections were also inspected for availability or physical damage. The condition of remote handling devices, source holders, well liners and 99Mo breakthrough kits were inspected. All additional standard sealed sources were checked. Finally, operation and service manuals, and instrument log-book were located. 3.4.2 Performance checks The daily performance checks on both radionuclide calibrators included auto zero, a background check, high voltage test and constancy checks. 40 University of Ghana http://ugspace.ug.edu.gh Without the presence of any radionuclide source in the well chamber or its vicinity, the key for daily performance checks was selected. Auto zero check was initiated and the displayed millivolt reading was recorded. The background check was initiated by choosing ―next test‖ from the prompt options at the finish of auto zero check. The minimum background activity of the system was accepted and noted. Auto zero and background tests make it possible to identify any eventual residual contamination in the well of the detector. Finally, high voltage test was initiated and the stable reading of the displayed system biasing voltage was noted. For battery alimented detectors, this test makes it possible to verify if the biasing volatge is within tolerance to avoid the recombination region.These tests were done on daily basis and the mean values were compared with manufacturer’s specifications within their stated tolerance. Results were tabulated. 3.4.3 Constancy check This test was done in addition to the daily auto zero, background and system tests. A long-lived 137Cs standard radionuclide source in vial form (source number NK 581) of activity 9.21 MBq (248.92 µCi) calibrated for 13th October, 2005 and manufactured by AEA Technology QSA GmbH was used for this check. The appropriate operating conditions for data check were selected. The background at the 137Cs setting was noted. With the aid of forceps, the check source was placed into the source holder and gently lowered into the well chamber of the calibrator. The reading was noted after 10s. 10s was chosen because it gives an optimum value of the response time for Capintec and Comecer dose calibrators (see Table 3.1). The net 41 University of Ghana http://ugspace.ug.edu.gh result was obtained by subtracting the background from the measurement. The result was recorded and this procedure was repeated three times. The mean and its associated standard deviation were calculated. Relative response test was also done with the 137Cs check source assayed at the 137Cs, 99mTc, 57Co, 131I, 67Ga, 133Xe and 201Tl radionuclide settings taking into account the background for each radionuclide window. The net readings were then recorded. The test was done once every week and the results were tabulated. 3.4.4 Accuracy test The appropriate operating conditions were selected for the 137Cs standard radionuclide source. The background at this setting was noted. With the aid of forceps, the 137Cs standard radionuclide source of activity 9.21 MBq (248.92 µCi) was placed into the source holder and gently lowered into the well chamber of the calibrator. The net reading was noted after 10s.The procedure was repeated three times and the mean of the measured activity was compared to the decay-corrected activity of the check source. Accuracy was calculated using the formula; ( ) 3.4.5 Linearity test A 10ml vial containing 773 mCi (28.6 GBq) of 99mTc prepared from the eluate of a fresh generator whose molybdenum breakthrough test was 0.023 µCi/mCi was used for this test. The appropriate operating conditions for 99mTc radionuclide were selected on the calibrator and the background was noted at this setting. With the use 42 University of Ghana http://ugspace.ug.edu.gh of forceps, a 10ml vial containing 99mTc source activity was placed into the source holder and gently lowered into the chamber well of the calibrator. The stable reading was recorded after 10s. The measured activity, time and date were noted. The activity was then assayed after 2, 6, 18, 30, 36, 40, 42, 48, 68, 74 and 94 hours respectively. For each assay; the background, measured activity, date and time were recorded. The expected activity of 99mTc was calculated for each time elapsed and the results were tabulated. 3.4.6 Geometry test The constant activity method was employed in this study. This involved the addition of gravimetrically determined cumulative volume (10-100%) of non-radioactive saline solution to a sample volume of known 99mTc activity in a vial or syringe. The appropriate operating conditions for 99mTc radionuclide were selected on the calibrator and the background was noted at this setting. To ensure reproducibility in the source geometry, the same source holder was used throughout the test and the vial/syringe placed in the center of the source holder. For Comecer dose calibrator the correct geometry (vial or syringe) was also chosen from the console. A 10 ml vial containing 1ml of 99mTc activity 56.67 mCi was placed into the sample holder with the aid of forceps. The vial was gently lowered into the chamber well and the reading was recorded after 10s. The measured activity and time was noted for both calibrators. The 10ml vial was removed from the chamber well and 0.5 ml of non-radioactive saline solution was carefully added to it using a 2 cc syringe. To help dilute the source volume easily and to avoid bubble formation, a bent needle was 43 University of Ghana http://ugspace.ug.edu.gh inserted into the septum of the vial. The vial was then assayed in the calibrator. The measured activity, time and volume of saline were noted for both calibrators. This procedure was repeated each time increasing the volume of saline solution in steps of 0.5ml until the vial reached a total volume of 6 ml. This procedure was now repeated with 1.66 mCi and 1.81 mCi of 99mTc activity in 2cc and 5 cc syringes respectively. The mean of the measured activity was compared with the decay- corrected activity for each volume and time elapsed. Volume correction factors (VCF) were calculated using the equation: ( ) The 3mL sample volume was chosen as reference volume for the calculation of VCFs for the 10mL vial while the 1mL was chosen for the 2 cc and 5 cc syringes respectively. 3.4.7 Contamination test This test was performed twice every week. This involved measuring the background at the 137Cs setting to check the dipper and/or well liner for any residual contamination at the end of a work day. Without the presence of any radionuclide source in the well chamber or its vicinity, the 137Cs window selected. The background at this setting was noted with the dipper (source holder) and liner in the well. The dipper was removed from the well and the background activity was noted. Finally, the well liner was also removed and the background noted. The liner was returned to the well to avoid contaminating the 44 University of Ghana http://ugspace.ug.edu.gh chamber well. The amount of contamination was calculated from the differences between the background activities with and without liner and dipper. 3.4.8 Other Statistical methods Statistical analysis was performed to clean out outliers from random data using the maximum minimum criterion of inclusion. In certain instances the data was normalized to a value of interest (e.g. mean, true value etc.) within the specified error margin of standard protocols for the test. Regression analysis was performed to find the extent to which the dependent is influenced by independent variable. T-test was also used for score variations and p-value was calculated to show if there is any significant impact of a test. Finally results were validated and the developed model was also assessed practically. 45 University of Ghana http://ugspace.ug.edu.gh CHAPTER FOUR RESULTS AND DISCUSSIONS In this chapter, the results obtained from chapter three are discussed. The results are categorized into quality control, performance evaluation, cross-calibration and validation of results. 4.1 Quality Control Table 4.1: Physical inspection Nature of inspection Comecer system Capintec system Housing/physical damage No damages No damages Power supply Compatible Compatible Remote handling devices, Two available and in Two available and in good good condition condition Source holders One available, not broken Three available, one is broken Well liners Available Available 99 Mo breakthrough kit Available and in good Available and in good condition condition Only 137 Standard Sealed Sources Cs standards Only 137Cs standards available available User/service manuals available available Instrument log-book Reccords not found Reccords not found 46 University of Ghana http://ugspace.ug.edu.gh As seen in Table 4.1, both calibrators were found in acceptable conditions with regards to physical inspection checks according to recommendations by IAEA- TECDOC-602 (1991). However, the instrument log book could not be found for both systems. 4.2 Daily quality control Table 4.2: Daily tests on Capintec Test Result Criterion Remark Auto Zero (mV) 0.049 ± 7.14% ± 0.05 mV passed Background (µCi) 52.90 ± 7.72 µCi 27-500 µCi passed High voltage test(V) 0-0.15 155 ±15.5 V failed 162.6-162.9 155 ±15.5 V passed Data Check 191.9± 2.6% ±5% or ±10% passed Cs-137 (µCi) With the evaluation criterion stipulated by Capintec (2007 and 2015) operation and service manuals, and recommendations given in IAEA TRS 454 (2006) and IAEA- TECDOC-602 (1991), daily performance tests for Capintec were within acceptable limits. However, it was observed that the high voltage test failed for five cases. This could have been due to an inherent inaccuracy in the electrometer leading to failure in registering bias voltage. Despite the electrometer failure, all data checks with 137Cs standard radionuclide source were found to be within the acceptable tolerance of ±5% indicating the presence of proper biasing voltage. This was an indication of drifts in the electronics of Capintec system. 47 University of Ghana http://ugspace.ug.edu.gh Table 4.3: Daily tests on Comecer Test Result Criterion Remark System Background 20.20 ± 8.61% ±20% passed High voltage test(V) 500 500 passed Data Check 191.87 ±1.62% ±5% or passed Cs-137 (µCi) ±10% With the evaluation criterion stipulated by Comecer ( 2010) operation and service manuals and the recommendations given IAEA TRS 454 (2006) and IAEA- TECDOC-602 (1991), it was observed that all daily performance tests on Comecer dose calibartor were within acceptable limits. 4.3 Constancy check Table 4.4: Constancy check on Comecer and Capintec systems 137 Cs Activity (µCi) Comecer Capintec Measured Mean activity 185.1±1.2% 193.7±0.74% SD 2.2 1.4 With the tolerance levels of ±5% recommended by IAEA TRS 454 (2006), both Comecer and Capintec dose calibrators were found to be within acceptable deviations of 1.2% and 0.74% for constancy test using 187.8 µCi of 137Cs standard radionuclide source. This indicated that Capintec had better reproducibility than Comecer in terms of assaying 137Cs standards. The mean activities of 137Cs source with the associated standard deviations for Comecer and Capintec over a period of 18 weeks were found to be 185.1±2.4 µCi and 193.7±1.4 µCi respectively. 48 University of Ghana http://ugspace.ug.edu.gh As also seen in Figure 4.1 (a) and (b), constancy check with 137Cs standard radionuclide source over the entire period shows linearity indicating that both systems had reproducibility within the ±5% acceptable tolerance levels as required by well-established international protocols (IAEA TRS 454, 2006 and IAEA- TECDOC-602, 1991). Capintec Comecer Comecer Capintec True value 196.0 194.0 1.050 192.0 190.0 1.025 188.0 1.000 186.0 184.0 0.975 182.0 180.0 0.950 0 5 10 15 20 0 5 10 15 20 Week Week (a) (b) Figure 4.1: (a) Graph of activity against number of weeks for constancy check (b) Relative deviation against number of weeks for constancy check on Comecer and Capintec dose calibrators. 4.4 Relative response check Table 4.5: Relative response to 137Cs radionuclide source 137 Cs Activity (µCi) Comecer reading (µCi) Capintec reading (µCi) Radionuclide window Mean SD Mean SD 137Cs 6.90±1.22% 0.08 7.30±4.50% 0.30 57Co 12.23±0.84% 0.10 21.60±5.00% 1.10 99mTc 14.17±1.06% 0.15 29.10±5.00% 1.60 67Ga 11.80±1.01% 0.12 24.40±2.50% 1.60 131I 10.33±0.65% 0.07 15.30±4.00% 0.60 201Tl 7.42±8.68% 0.64 9.10±6.10% 0.60 49 Cs-137 Activity (µCi) Relative deviation University of Ghana http://ugspace.ug.edu.gh With tolerance levels of ±5% recommended by ANSI N42.13 (2004), both systems were within acceptable limits for relative response to 137Cs standard radionuclide source at 137Cs, 57Co, 99mTc, 67Ga and 131I radionuclide settings. Comecer was found to have better reproducibility as compared to Capintec with regards to relative response at these radionuclide settings. However, it was observed that both Comecer and Capintec systems had unacceptable deviations of 8.68% and 6.10% at the 201Tl radionuclide setting respectively. This could have been due to a wrong gain setting at this radionuclide setting. Cs-137 Co-57 Tc-99m Cs-137 Co-57 Tc-99m Ga-67 I-131 Tl-201 Ga-67 I-131 Tl-201 15 13 29 25 11 21 9 17 7 13 5 9 3 5 1 1 1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10 Days Days (a) (b) Figure 4.2: (a) Relative response test for Comecer and (b) Relative response test for Capintec using 137Cs standard radionuclide source. Figure 4.2 (a) and (b) above show stable readings with time for both Comecer and Capintec with regards to relative response to 137Cs standards at the radionuclide settings used. This indicated that both systems have good relative response within acceptable tolerance levels. 50 Cs-137 Activity (mCi) Cs-137 Activity (mCi) University of Ghana http://ugspace.ug.edu.gh 4.5 Accuracy test Table 4.6: Accuracy of Comecer and Capintec Cs-137 activity (µCi) Comecer Capintec Expected activity 187.8 187.8 Measured Mean activity 185.1±1.4% 193.7±3.1% With regards to accuracy in the measurement of 187.8 µCi of 137Cs standard radionuclide source over a period of 18 weeks the mean of the measured activities with the associated uncerntainties for Comecer and Capintec dose calibrators were found to be 185.1 µCi ±1.4% and 193.7 µCi ±3.1% respectivey. As seen from the results for accuracy test in Table 4.6 both dose calibrators were well within the ±5% tolerance level recommended by IAEA TRS 454 (2006). Capintec Comecer True value Comecer Capintec True value 200 1.100 196 1.050 192 188 1.000 184 0.950 180 0.900 0 5 10 15 20 0 5 10 15 20 Week Week (a) (b) Figure 4.3: Measured 137(a) Cs activities against number of weeks (b) Deviations of measured activity about the true activity of 137Cs standard radionuclide source. 51 Cs-137 Activity (µCi) Relative Value University of Ghana http://ugspace.ug.edu.gh The graphs in Figure 4.3 (a) and (b) above also indicate that the accuracy in the measurement of 137Cs standard radionuclide source on both Comecer and Capintec dose calibrators were well within a ±5% tolerance. 4.6 Linearity response Table 4.7: Linearity response for Comecer to 99mTc radionuclide source Time Background e l a psed Net measured Expected Date (mCi) (hrs.) Activity(mCi) Activity(mCi) 18-11-17 0.02 0.00 773.02± 0.00% 773.02 18-11-17 0.02 2.15 602.56± 0.10% 603.01 18-11-17 0.02 6.10 380.56± 0.40% 382.07 19-11-17 0.02 18.00 97.52± 0.90% 96.63 19-11-17 0.02 24.10 48.76± 2.10% 47.75 19-11-17 0.02 30.15 24.40± 2.80% 23.74 20-11-17 0.02 36.13 12.19± 2.50% 11.89 20-11-17 0.02 40.06 7.75± 2.50% 7.56 20-11-17 0.02 42.26 6.01± 2.60% 5.86 20-11-17 0.02 48.69 2.88± 3.20% 2.79 21-11-17 0.02 67.94 0.36± 16.10% 0.31 21-11-17 0.02 74.46 0.16 ± 6.70% 0.15 22-11-17 0.02 93.94 0.017±13.20% 0.015 With tolerance levels of ±5% recommended by IAEA (TRS 454, 2006) and ANSI N42.13 (2004) for linearity test, Comecer was found to have linearity response within acceptable limits for 99mTc activities above 1mCi. For 99mTc below 1 mCi the system had unacceptable deviations and this could have been due to its low measurement resolution of 4.1 µCi (Comecer, 2010). Comecer was found to underestimate 99mTc assays below 1 mCi by 13-16%. This agrees with Vargas et al (2018) who have reported significant underestimation of 99mTc activity by 10–20% resulting from measurements using Comecer dose 52 University of Ghana http://ugspace.ug.edu.gh calibrators of the type VDC-405 and VDC-404. However, the activities underestimated were below the useful clinical range and as such cannot be the reason for not using Comecer for clinical assays. Table 4.8: Linearity response for Capintec to 99mTc radionuclide source Time Background elapsed Net measured Expected Date (mCi) (hrs.) Activity(mCi) Activity(mCi) 18-11-17 0.91 0.00 871.10±0.00% 871.10 18-11-17 0.64 2.12 676.40±0.80% 681.90 18-11-17 0.46 6.04 398.50±8.10% 433.50 19-11-17 0.65 18.04 106.50±1.80% 108.4 19-11-17 0.75 24.04 52.60±2.90% 54.19 19-11-17 0.77 30.09 26.20±2.60% 26.90 20-11-17 0.76 36.07 13.10±3.00% 13.50 20-11-17 0.71 40.00 8.37±2.30% 8.57 20-11-17 0.72 42.17 6.47±3.00% 6.67 20-11-17 0.77 48.60 3.19±0.60% 3.17 21-11-17 0.72 67.82 0.32±5.90% 0.34 21-11-17 0.78 74.30 0.17±6.30% 0.16 22-11-17 0.66 93.73 0.016±5.90% 0.017 With the tolerance level of ±5% recommended by IAEA (TRS 454, 2006) and ANSI N42.13 (2004) for linearity test, Capintec was also found to have linearity response within acceptable limits for 99mTc activities above 1 mCi. Despite Comecers’ better regression coeficient than Capintec, the study found Capintec to have better measurement resolution for activities below 1 mCi. This could have been due to its higher measurement resolution of 0.027 µCi as compared to the 4.1 µCi for Comecer system (Comecer, 2010 and Capintec, 2007). 53 University of Ghana http://ugspace.ug.edu.gh 99mTc DECAY CURVES 900 y = 747.53e-0.113x800 Comecer R² = 0.9996 700 Capintec 600 500 400 y = 851.9e-0.116x 300 R² = 0.9999 200 100 0 0 10 20 30 40 50 60 70 80 90 Time (hrs) Figure 4.4: Decay curves for 99mTc activities on Capintec and Comecer The decay curves for 99mTc both Capintec and Comecer systems were found to be exponential as expected and this was an indication the laws of radioactivity (see Figure 4.4). As also seen in Figure 4.5, both systems showed good linearity response within acceptable limits with good regression coeficients. 7.00 y = -0.1132x + 6.6168 Capintec 6.00 R² = 0.9996 Comecer 5.00 4.00 3.00 2.00 1.00 y = -0.1157x + 6.7475 R² = 0.9999 0.00 -1.00 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 -2.00 Time (hours) -3.00 -4.00 -5.00 Figure 4.5: Linearity Response for Capintec and Comecer dose calibrators on logarithmic scale. 54 Relative Tc-99m Activity (log Tc-99m Activity (mCi) scale) University of Ghana http://ugspace.ug.edu.gh Despite showing good linearity response, the study further revealed overestimation of 99mTc assays by Capintec as shown in Figure 4.6 (a) and (b). 4.6.1 99mOverestimation of Tc assays by capintec 35.00 35.00 30.00 30.00 25.00 25.00 20.00 20.00 15.00 15.00 10.00 10.00 5.00 5.00 0.00 0.00 5 10 15 20 25 30 35 40 45 0 200 400 600 800 Comecer Tc-99m Activity (mCi) Comecer Tc-99m Activity (mCi) (a) (b) Figure 4.6: (a) % of 99mTc activity overestimated by Capintec over entire range of activities used and % of 99m(b) Tc activity overestimated by Capintec over useful clinical range. From the results for linearity test, the difference between corresponding 99mTc assays with decay for Capintec and Comecer was calculated and the result was expressed as a percentage of the indicated activity for Comecer. This was the percentage of 99mTc assay overestimated by Capintec. As seen in Figure 4.6 (a) and (b) above, Capintec was found to overestimate 99mTc assays by 11-31%. These observations led to further investigation of the effects of ion recombination and chamber residual contamination. 55 Capintec overestimation % Capintec overestimation % University of Ghana http://ugspace.ug.edu.gh 4.6.1 Capintec electrometer inacuracy 1.1 Capintec Ideal line 1.05 1 0.95 0.9 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 Tc-99m True activity (GBq) Figure 4.7: Drifts in Capintec electrometer readings As can be seen from Figure 4.7 above, the ratio of the measured to expected activity for Capintec was found to <1 for 99mTc activities above 1 mCi. This indicated drifts in the electrometer readings for Capintec. As seen in Table 4.2 of the results for daily tests, Capintec electrometer failed to register the bias voltage for some tests. This gave a force impression of charge losses (due to ion recombination) for Capintec. This could have been the reason for unusually high background readings at the 99mTc and 137Cs radionuclide settings for Capintec. According to Gadd et al (2006), for most commercial dose calibrators, the effects of ion recombination should be less than 1% when measuring 100 GBq of 99mTc. As seen in Figure 4.7, the ratio of the indicated to true activity approached 1 for 99mTc source activities above 22 GBq and as such any recombination could have still being within the 1% tolerance. 56 Measured /Expeted University of Ghana http://ugspace.ug.edu.gh 4.6.2 Effects liner and/or dipper residual contamination Dipper+liner liner only without dipper+liner 500 400 300 200 100 0 1 2 3 4 5 6 7 8 9 10 No. of weeks Figure 4.8: Effects of residual contamination for Capintec Figure 4.8 above indicates that the background readings did not differ significantly with presence of liner and/or dipper. The mean of background readings with their associated standard deviations for dipper+liner, liner only and without dipper+liner configurations for Capintec at the 137Cs setting were found to be 419.0±26.4 µCi, 420.0±26.6 µCi and 419.0±23.4 µCi respectively. The dipper and liner contamination levels were calculated for each week and the results are shown in Figure 4.9 below. 57 Activity(µCi) University of Ghana http://ugspace.ug.edu.gh Dipper Liner 9 8 7 6 5 4 3 2 1 0 0 2 4 6 8 10 Weeks Figure 4.9: Dipper and liner contamination levels for Capintec The liner and dipper were found to have contamination levels of 1-8µ Ci and 1-3 µCi respectively. However, these results were below Capintec acceptable background range (27-500 µCi) which indicated that residual contamination was not the reason for the usually high background at the 137Cs and 99mTc radionuclide settings. The study also found non-linearity in the electronics of Capintec since the ratio of the measured response to the true response was not constant over the range of current inputs for calibrator which could have arisen from the electrometer’s inherent inaccuracy. This could have led to a wrong gain at the 137Cs and 99mTc radionuclide setting which gave a high background reading. 58 Activity (µCi) University of Ghana http://ugspace.ug.edu.gh 4.7 Geometry test Table 4.9: Geometry dependence for Comecer and Capintec dose calibrators Comecer Activity (mCi) 10ml vial 5ml syringe 2ml syringe Mean Meaured 54.90±0.44% 1.76±1.68% 1.64±0.36% Expected 54.66 1.79 1.65 Capintec Mean Meaured 54.98±0.51% 1.71±1.16% 1.71±0.35% Expected 54.70 1.73 1.72 Table 4.9 above shows the deviation of the measured from expected (decay- corrected) activities of 99mTc activity using different sample geometries. With regards to geometry dependence on Comecer the uncertainties introduced by the 10mL vial, 5mL and 2mL syringe geometry were found to be 0.44%, 1.68% and 0.36% indicating that the results were within tolerance levels. Similarly, the influence of geometry on Capintec for the 10mL vial, 5mL and 2mL syringes used were found to be 0.51%, 1.16% and 0.35% respectively. Therefore, with the tolerance levels of ±5% recommended by well-established international protocols, both systems passed geometry test (IAEA TRS 454, 2006). 59 University of Ghana http://ugspace.ug.edu.gh Capintec Comecer 1.040 1.030 y = 0.0104x + 0.973 R² = 0.9818 1.020 1.010 1.000 0.990 y = 0.0118x + 0.9635 R² = 0.9454 0.980 0.970 0.960 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 Volume(mL) Figure 4.10: Volume correction factor against sample volume for Comecer and Capintec dose calibrators using a 10ml vial. With regards to volume correction factors (VCF) for the 10ml vial, both calibrators had factors within the recommended 0.955%. In addition to both calibrators passing this test, VCFs were determined and it was revealed that both systems had factors within the acceptable range of 0.95