Fundamentals of Nuclear Pharmacy

300 Pages·1984·37.484 MB·English

by  Gopal B. Saha Ph.D. (auth.)

Fundamentals of Nuclear Pharmacy
Gopal B. Saha
Fundamentals
ofN uclear Pharmacy
Second Edition
With 91 Illustrations
Springer Science+Business Media, LLC
GOPAL B. SAHA, Ph.D.
Professor and Director of Radiopharmacy
College of Pharmacy
University of New Mexico
Albuquerque, New Mexico
Library of Congress Cataloging in Publication Data
Saha, Gopal B.
Fundamentals of nuclear pharmacy.
Bibliography: p.
Includes index.
1. Radiopharmaceuticals. I. Title. [DNLM:
1. Nuclear medicine. 2. Pharmacy. 3. Radioisotopes. WN
440 S 131 fI
RM852.S23 1983 615.8'42 83-10381
© 1984 Springer Science+Business Media New York
Originally published by Springer-Vedag New York, Inc. in 1984
Softcover reprint of the hardcover 2nd edition 1984
All rights reserved. No part of this book may be translated or reproduced in any form
without written permission from Springer Science+Business Media, LLC.
The use of general descriptive names, trade names, trademarks, etc., in this
publication, even if the former are not especially identified, is not to be taken as
a sign that such names, as understood by the Trade Marks and Merchandise
Marks Act, may accordingly be used freely by anyone.
Typeset by Ampersand Inc., Rutland, Vermont
9 8 765 432
ISBN 978-1-4757-4026-4 ISBN 978-1-4757-4024-0 (eBook)
DOI 10.1007/978-1-4757-4024-0
To my wife, Sipra
and
my children, Prantik and Trina
Contents
Foreword .................................................. xiii
Preface to the Second Edition ....................... . . . . . . . . . . xv
Preface to the First Edition ................................... xvii
Chapter 1 The Atom ................................... 1
Electronic Structure of the Atom .............................. 1
Chemical Bonds ............................................ 3
Electrovalent Bond ........................................ 5
Covalent Bond ............................................ 5
Coordinate Covalent Bond ................................. 5
Complex Formation ....................................... 6
Structure of the Nucleus ..................................... 7
Questions .................................................. 10
Suggested Reading .......................................... 11
Chapter 2 Radioactive Decay ......................... 13
Decay of Radionuclides ...................................... 13
et Decay................................................. 13
f3- Decay ................................................ 13
Positron or f3+ Decay ...................................... 14
Electron Capture (EC) ..................................... 16
Isomeric Transition (IT) ................................... 17
Radioactive Decay Equations ................................. 19
General Equation ......................................... 19
Half-Life and Mean Life ................................... 20
Units of Radioactivity ..................................... 21
Calculations .............................................. 23
Successive Decay Equations .................................. 24
General Equation ......................................... 24
Transient Equilibrium ..................................... 25
Secular Equilibrium ....................................... 27
Statistics of Counting ........................................ 27
Error, Accuracy, and Precision ............................. 28
Standard Deviation ........................................ 29
Standard Deviation of Count Rates .......................... 30
viii Contents
Propagation of Errors ...................................... 30
Distribution of Counting Time .............................. 31
Questions .................................................. 32
Suggested Reading .......................................... 33
Chapter 3 Production of Radionuclides 35
Cyclotron-Produced Radionuclides ............................ 35
Short-Lived Radionuclides .................................. 39
Reactor-Produced Radionuclides .............................. 40
Fission or (n,t) Reaction ................................... 41
Neutron Capture or (n;y) Reaction .......................... 42
Target and Its Processing .................................... 43
Equation for Production of Radionuclides ...................... 43
Specific Activity ............................................ 50
Questions .................................................. 51
Suggested Reading .......................................... 52
Chapter 4 Radionuclide Generators ................... 53
Principles of a Generator . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Important Radionuclide Generators ............................ 56
99Mo_99mTc Generator ............ " . . . . . . . . .. . . . . . . . . . . . . . 56
1l3Sn_113mIn Generator .................................... 64
68Ge_68Ga Generator. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . .. .. . . 64
87y_87mSr Generator ...................................... 65
Questions .................................................. 65
Suggested Reading .......................................... 66
Chapter 5 Radiopharmaceuticals and Instruments ..... 67
Ideal Radiopharmaceutical ................................... 68
Easy Availability ......................................... 68
Short Effective Half-Life ................................... 68
No Particle Emission ...................................... 69
Decay by Electron Capture or Isomeric Transition ............. 70
High Target-to-Nontarget Activity Ratio ..................... 71
Metabolic Suitability ...................................... 71
Dosage Forms .............................................. 71
Design of New Radiopharmaceuticals .......................... 72
General Considerations .................................... 72
Factors Influencing the Design of New Radiopharmaceuticals ... 73
Gamma-Ray Detecting Instruments ............................ 77
Collimator ............................................... 78
Detector ................................................. 78
Photomultiplier Tube ...................................... 79
Preamplifier .............................................. 79
Linear Amplifier .......................................... 80
Contents ix
Pulse Height Analyzer ..................................... 80
Display or Storage ........................................ 80
Scintillation Camera ......................................... 81
Collimator ............................................... 81
Detector ................................................. 83
X,Y Positioning Circuit .................................... 83
Pulse Height Analyzer .................................... 84
Display or Storage ........................................ 84
Questions .................................................. 85
Suggested Reading .......................................... 86
Chapter 6 Radiolabeling of Compounds. . . . . . . . . . . . . . . . 87
Methods of Labeling ......................................... 87
Isotope Exchange Reactions ................................ 87
Introduction of a Foreign Label ............................. 88
Labeling with Bifunctional Chelates .......................... 88
Biosynthesis or Chemical Synthesis .......................... 89
Recoil Labeling ........................................... 89
Excitation Labeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
Important F actors in Labeling ................................ 90
Efficiency of the Labeling Process ........................... 90
Chemical Stability of the Product ........................... 90
Denaturation or Alteration ................................. 90
Isotope Effect ............................................ 90
Carrier-Free or No-Carrier-Added (NCA) State. . . . . . . . . . . . . . . 91
Storage Conditions ........................................ 91
Specific Activity .......................................... 91
Radiolysis .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Purification and Analysis ................................... 92
Shelf Life ................................................ 92
Specific Methods of Labeling ................................. 92
Radioiodination ........................................... 93
Labeling with 99mTc 96
Structure of 99m Tc-Complexes .............................. 99
Kits .................. .................................. 100
Colloids and Labeled Particles ................................ 101
Additives .................................................. 102
Questions .................................................. 103
Suggested Reading .......................................... 104
Chapter 7 Characteristics of Specific
Radiopharmaceuticals .................................... 105
99mTc-Labeled Compounds ................................... 105
99mTc-Labeled Human Serum Albumin. . . . . . . . . . . . . . . . . . . . . . . 105
99mTc-Labeled Macroaggregated Albumin .................... 106
x Contents
99mTc-Labeled Albumin Microspheres ........................ 106
99mTc-Phosphate Compounds ............................... 107
99mTc-Sulfur Colloid ....................................... 108
99mTc-DTPA ............................................. 109
99mTc-Labeled Red Blood Cells ............................. 110
99mTc-Labeled Imunodiacetic Acid Derivatives ................ 110
Other 99mTc-Labeled Compounds ........................... 111
Radioiodinated Compounds ................................... 112
131 I-Sodium Iodide ........................................ 112
123I-Sodium Iodide ........................................ 115
1251_, 13lI-Labeled Albumin ................................. 115
1311-Labeled Macroaggregated Albumin ...................... 115
131 I-Rose Bengal .......................................... 116
131 I-Sodium Orthoiodohippurate ............................. 117
1311-Labeled 19-Iodocholesterol and
6fJ-Iodomethyl-19-Norcholesterol ........................... 117
1311_ or 125I-Labeled Fibrinogen ............................. 117
Miscellaneous Compounds of Clinical Interest .................. 118
75 Se-Selenomethionine ..................................... 118
II1 In- or 113mln_DTPA ..................................... 118
Macroaggregated 113mln(OH)rFerric Hydroxide. . . . . . . . . . . .... 120
133Xe and 85Kr ........................................... 120
18F-Sodium Fluoride ...................................... 120
201TL-Thallous Chloride ................................... 120
32p-Sodium Phosphate ..................................... 120
57 Co- or 58 Co-Cyanocobalamin ............................. 121
II1 In-Labeled Platelets and Leukocytes ....................... 121
51 Cr-Labeled Red Blood Cells .............................. 121
57 Co- or III In-Bleomycin ................................... 123
Other Compounds of Clinical Importance .................... 123
Questions .................................................. 123
Suggested Reading .......................................... 124
Chapter 8 Quality Control of
Radiopharmaceuticals .................................... 125
Physicochemical Tests ....................................... 126
Physical Characteristics .................................... 126
pH and Ionic Strength ..................................... 127
Radionuclidic Purity ....................................... 127
Radiochemical Purity ...................................... 128
Chemical Purity .......................................... 139
Radioassay ............................................... 140
Biological Tests ............................................. 141
Sterility .................................................. 141
Apyrogenicity ............................................ 144
Contents xi
Toxicity ................................................. 146
Record Keeping ............................................. 146
Questions .................................................. 147
Suggested Reading .......................................... 148
Chapter 9 Nuclear Pharmacy .......................... 149
Concept ................................................... 149
Design of a Nuclear Pharmacy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Operation of a Nuclear Pharmacy ............................. 153
Receiving of Radioactive Packages .......................... 153
Preparation of Radiopharmaceuticals ....... . . . . . . . . . . . . . . . . . . 154
Quality Control of Radiopharmaceuticals ..................... 155
Storage .................................................. 156
Dispensing ............................................... 156
Radioactive Waste Disposal ................................ 157
Centralized Nuclear Pharmacy ................................ 157
Questions .................................................. 159
Suggested Reading .......................................... 159
Chapter 10 Radiation Dosimetry, Protection, and
Regulations 161
Radiation Units ............................................. 161
Radiation Dosimetry ........................................ 163
Radiation Dose in SI Units ................................. 166
Radiation Protection ......................................... 167
Maximum Permissible Dose ................................ 167
Nonoccupationally Exposed Personnel ....................... 171
Principles of Radiation Protection ........................... 171
Personnel Monitoring ...................................... 173
Survey Meters ............................................ 175
Waste Disposal ........................................... 176
Dos and Don'ts in Radiation Protection Practice .............. 177
Radiation Regulations ....................................... 177
Nuclear Regulatory Commission (NRC) ...................... 178
Food and Drug Administration (FDA) ....................... 178
Department of Transportation (DOT) ........................ 179
Nuclear Pharmacies ....................................... 180
Questions .................................................. 184
Suggested Reading .......................................... 184
Chapter 11 In Vitro and In Vivo Nonimaging Tests.. . 187
Radioimmunoassay .......................................... 187
Principle ................................................. 187