textbook of radiopharmacy
TRANSCRIPT
TEXTBOOK OF RADIOPHARMACY
Theory and Practice
SECOND EDITION
Edited by
CHARLES B. SAMPSON Addenbrooke's Hospital
Cambridge, UK
B Gordon and Breach Publishers Australia • Austria • China • France • Germany • India • Japan • Luxembourg • Malaysia • Netherlands • Russia • Singapore • Switzerland • Thailand • United Kingdom • United States
CONTENTS
ireword to the Second Edition xii
eface to the First Edition xiii
eface to the Second Edition xv
it of Contributors xvi
SECTION I Theoret ica l aspects
1. BASIC PRINCIPLES OF RADIONUCLIDE PHYSICS 1 M.D. Short
1.1 Introduction 1 1.2 Basic concepts of ionising radiation 1 1.3 Structure of the atom and nucleus 2 1.4 Radionuclides and modes of decay 4 1.5 Radionuclide decay schemes 6 1.6 Radioactive decay law 8 1.7 Units of radioactivity 10 1.8 Interaction of radiation with matter 10 1.9 Radionuclide production 14 1.10 Summary of physical data for selected radionuclides 16 1.11 Further reading 17
2. RADIONUCLIDE GENERATORS 19 A.T. Elliott
2.1 Introduction 19 2.2 Theory of a generator system 19 2.3 Radionuclide separation techniques 20 2.4 Generator systems 21 2.5 Routine quality control 26 2.6 Problems 27 2.7 Conclusion 28 References 28
3. PHYSICO-CHEMICAL CONCEPTS IN THE PREPARATION OF TECHNETIUM RADIOPHARMACEUTICALS 29 D.P. Nowotnik
3.1 Introduction 29 3.2 Chemistry of technetium 29 3.3 Technetium cold kit components 32 3.4 Technetium complexes in nuclear medicine 33 3.5 The preparation of technetium radiopharmaceuticals 42 3.6 The importance of specific activity and radiolysis 43 3.7 Conclusions 43 References 44
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SECTION II Practical radiopharmaceutics
4. DESIGN OF HOSPITAL RADIOPHARMACY LABORATORIES CR. Lazarus
4.1 Introduction 4.2 Aims of radiopharmacy design 4.3 Factors to be considered in radiopharmacy design 4.4 Recommendations 4.5 Conclusions Further reading
5. TECHNIQUES FOR DISPENSING OF RADIOPHARMACEUTICALS CR. Lazarus
5.1 Introduction 5.2 General working procedures 5.3 'Open' and 'Closed' procedures 5.4 Dispensing procedures 5.5 Use and maintenance of contained workstations 5.6 Conclusions Further reading References
6. RADIOLABELLING OF BLOOD CELLS - THEORY HJ. Danpure and S. Osman
6.1 Introduction 6.2 Properties of an ideal cell labelling agent 6.3 Chelating agents used in cell labelling 6.4 Choice of radionuclide 6.5 Parameters required for successful cell labelling 6.6 Health and safety aspects in working with blood cells References
7. RADIOLABELLING OF BLOOD CELLS - METHODOLOGY HJ. Danpure and S. Osman
7.1 Introduction 7.2 Radiolabelling erythrocytes 7.3 Radiolabelling leucocytes 7.4 Radiolabelling platelets 7.5 Conclusions Acknowledgements References
8. RADIOLABELLED ANTIBODIES AS RADIOPHARMACEUTICALS S.J. Mather
8.1 Introduction 8.2 Tumour antigens 8.3 Antibody production 8.4 Characterisation of antibodies
in
Contents
8.5 Radiolabelled antibodies 89 8.6 Antibody analysis and quality control 92 8.7 Animal models for radiolabelled antibodies 95 8.8 Pharmacokinetic aspects of radiolabelled antibodies 96 8.9 Clinical uses of radiolabelled antibodies 98 8.10 Conclusion 98 References 100 Recommended further reading 101
9. QUALITY CONTROL OF RADIOPHARMACEUTICALS 103 A.E. Theobald
9-1 Introduction 103 9 2 Quality control parameters 104 9-3 Radiochemical purity determinations 109 9.4 Panicle sizing 122 9 5 Particulate contamination 123 9.6 Control of pH 123 9 7 Biological distribution tests 123 9.8 Summary and conclusions 123 References 123
10. FACTORS WHICH AFFECT THE INTEGRITY OF RADIOPHARMACEUTICALS 145 C. Hojelse, K. Kristensen and C.B. Sampson
10.1 Introduction 145 10.2 General defects 145 10.3 Registration of defects 150 10.4 Conclusion 150 References 151
11. DOCUMENTATION, LABELLING, PACKAGING AND TRANSPORTATION 153 A.M. Millar and K.E. Goldstone
11.1 Introduction 153 11.2 Documentation 153 11.3 Labelling 156 11.4 Packaging and transport 157 11.5 Summary of records to be kept in a radiopharmacy 159 References 159
12. MICROBIAL AND RADIATION MONITORING IN THE RADIOPHARMACY l6 l S.R. Hesslewood
12.1 Introduction l6 l 12.2 Sources of particulate contamination in radiopharmacies 161 12.3 Procedures for reducing microbial and particulate contamination 162 12.4 Consequences of particulate contamination of radiopharmaceuticals 163 12.5 Detection of microbial and particulate contamination in the radiopharmacy 164 12.6 Radioactive contamination of radiopharmacies 165 12.7 Monitoring of radioactivity levels in radiopharmacies 166 References 167
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WASTE MANAGEMENT IN THE RADIOPHARMACY 169 A.T. Elliott
13-1 Introduction 169 13-2 Radioactive waste management löl 13-3 Radioactive waste store 169 134 Disposal of radioactive waste 169 13.5 Records 17 References
OPERATOR SAFETY IN THE HANDLING OF RADIOPHARMACEUTICALS 17: S.R. Hesslewood
14.1 Introduction 173 14.2 Regulations and codes of practice 173 14.3 Handling of radioactive materials in the radiopharmacy 174 14.4 Personnel monitoring 176 14.5 Accidents in the radiopharmacy 178 14.6 Conclusions 180
REGULATORY REQUIREMENTS FOR THE DISPENSING AND SUPPLY OF RADIOPHARMACEUTICALS J.R. Gill and J.L. Turner
15.1 Introduction 181 15.2 The Medicines Act 1968 181 15.3 The Health and Safety at Work etc. Act 1974 185 15.4 The European Community 190 15.5 The preparation and supply of radiopharmaceuticals in the National Health Service 191 15.6 Summary 192 References 192 Further reading 192
OFFICIAL AND NON-OFFICIAL RADIOPHARMACEUTICALS AND THEIR PROPERTIES 193 P.J. Maltby
16.1 Introduction 193 16.2 Official radiopharmaceuticals 193 16.3 Non-official radiopharmaceuticals 198 16.4 Conclusion 200 Further reading 200
SECTION III Localisation and disposition of radiopharmaceuticals
17. MECHANISMS OF LOCALISATION OF RADIOPHARMACEUTICALS M. Frier
17.1 Introduction 17.2 Modes of localisation 17.3 Summary and conclusion References Further reading
201
201 201 206 206 207
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18. PHARMACOLOGY, PHARMACOKINETICS AND METABOLISM OF RADIOPHARMACEUTICALS M. Frier
18.1 18.2 18.3 18.4 18.5 18.6 18.7 18.8
Introduction Myocardial agents Skeletal agents Renal agents Particulate agents Brain blood flow agents Hepatobiliary agents Conclusion
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209 209 210 210 211 212 212 213
References 213
19. EFFECT OF PATIENT MEDICATION AND OTHER FACTORS ON THE BIODISTRIBUTION OF RADIOPHARMACEUTICALS 215 C.B. Sampson and P.H. Cox
19-1 Introduction 215 19.2 Classification of drug/radiopharmaceutical interactions 215 19-3 Effects of radiation therapy and other extraneous factors 224 19.4 Diet 226 19.5 Registration of instances of abnormal biodistribution 226 References 226
20. USE OF DRUGS TO ENHANCE NUCLEAR MEDICINE STUDIES 229 S.C.E. Leung and S.R. Hesslewood
20.1 Introduction 229 20.2 Cardiac studies 229 20.3 Renal studies 230 20.4 Hepatobiliary studies 231 20.5 Gastrointestinal studies 233 20.6 Adrenal studies 234 20.7 Brain studies 235 20.8 Thyroid studies 235 20.9 Conclusion 236 References 236
ECTION IV Clinical r ad iopha rmacy
21. DIAGNOSTIC APPLICATIONS OF RADIOPHARMACEUTICALS 243 L. Smith
21.1 Introduction 243 21.2 Imaging studies 243 21.3 Non-imaging studies 264 21.4 Conclusions 266 References 267 Further reading 267
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22. THERAPEUTIC APPLICATIONS OF RADIOPHARMACEUTICALS 2691 D.T. Murray and T.E. Hilditch
22.1 Introduction 269 j 22.2 Factors determining the effectiveness of radionuclide therapy 26S 22.3 Clinical applications 272 References 281
23. ADVERSE REACTIONS AND UNTOWARD EVENTS ASSOCIATED WITH THE USE OF RADIOPHARMACEUTICALS D.H. Keeling
23-1 Introduction 23-2 Definitions 23-3 Classification 23-4 Radiation effects 23.5 Pharmacology of hypersensitive reactions 23-6 Pyrogens 23.7 Sterility 23.8 Reporting schemes 23-9 Interpretation of reports 23.10 Results of reporting schemes 23-11 Incidence References
24. DOSIMETRIC ASPECTS M. Pillay
24.1 Introduction 24.2 Biological effects of radiation 24.3 Definitions and units 24.4 Parameters required for internal dose calculations Further reading
25. NEW RADIOPHARMACEUTICALS P.H. Cox and S.J. Mather
2 5 1 Introduction 25.2 Positron emitting radiopharmaceuticals 25.3 Single photon emitting radiopharmaceuticals 25.4 Generator systems for P.E.T. 25.5 New carrier molecules References
26. USE OF RADIOPHARMACEUTICALS IN THE EVALUATION OF DRUG FORMULATIONS J.G. Hardy
26.1 Introduction 26.2 Oral dosage forms 26.3 Rectal formulations 26.4 Ophthalmic formulations 26.5 Formulations for inhalation 26.6 Nasal formulations 26.7 Conclusion References
Contents
ACTION V Paediatr ic r ad iopha rmacy
27. PAEDIATRIC RADIOPHARMACY 327 K. Evans
27.1 Introduction 327 27.2 Administered doses 328 27.3 Preparation of doses and documentation 330 27.4 Immobilisation of children 331 27.5 Sedation 332 27.6 Injection techniques 332 27.7 Organ depth correction 332 27.8 Absorbed radiation dose 333 References 334 Further reading 337
tpendix A: Summary of decay parameters of some commonly used radionucliotides 339
»pendix B: Mean weight (kilogrammes) of babies and children 346
dex 347
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