Table Of ContentFundamentals of Nuclear Pharmacy
Fourth Edition
Springer Science+Business Media, LLC
Gopal B. Saha, Ph.D.
Director of Nuclear Chemistry and Pharmacy
Department of Nuclear Medicine
The Cleveland Clinic Foundation
Fundatnentals of
Nuclear Phannacy
Fourth Edition
With 113 illustrations
, Springer
Gopal B. Saha, Ph.D.
Director of Nuclear Chemistry and Pharmacy
Department of Nuclear Medicine
The Cleveland Clinic Foundation
Cleveland, OH 44195
USA
Library of Congress Cataloging-in-Publication Data
Saba, Gopal B.
Fundamentals of nuclear pharmacy / Gopal B. Saba. - 4th ed.
p. cm.
Includes index.
1. Radiopharmaceuticals. 2. Nuclear medicine. I. Title.
RS431.R34S24 1997
616.07'575--dc21 97-34137
Printed on acid-free paper.
ISBN 978-1-4757-2936-8 ISBN 978-1-4757-2934-4 (eBook)
DOI 10.1007/978-1-4757-2934-4
© 1998 Springer Science+Business Media New York
Originally published by Springer-Verlag New York, Inc in 1998.
Softcover reprint of the hardcover 4th edition 1998
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Preface
Since the third edition of The Fundamentals of Nuclear Pharmacy was pub
lished in 1992, radiopharmaceutical chemistry and various aspects of
nuclear medicine have experienced significant growth and development. The
new information plus the appreciation of the book in the nuclear medicine
community have prompted us to publish a new edition.
As with the past editions, this fourth edition is primarily based on the
contents of various courses given over several decades to nuclear pharmacy
students, nuclear medicine and radiology residents, and nuclear medicine
technology students. The book is written in chronological order from the
basic atomic structure to the clinical uses of radiopharmaceuticals. It serves
as a textbook on nuclear pharmacy for nuclear pharmacy and nuclear medi
cine technology students as well as a reference book for many professionals
interested in nuclear medicine, such as nuclear medicine physicians and
radiologists.
There are 15 chapters in the book. At the end of each chapter a set of
pertinent questions and some suggested reading materials are included.
Chapters 1 to 6 have only minor changes from previous editions, because
the materials in these chapters are basic in nature and do not change over
time. Some new radionuclides have been added to Table 4.1. Minor changes
in the section Design of New Radiopharmaceuticals and some additions in
99mTc chemistry have been made in Chapter 6. Chapter 7 is thoroughly
revised with obsolete radiopharmaceuticals removed and new and useful
ones included. Chapters 8 to 10 do not have any major changes, except in
Tables 8.1,8.2, and 10.1, which are updated for new radiopharmaceuticals.
Chapter 11 is a new chapter titled "Radiation Regulations and Protection,"
the contents of which are from the old Chapter 10 but with the inclusion
of all current changes in regulations. The radioimmunoassay section in
Chapter 12 has been revised slightly. Many changes have been made in
Chapter 13 to include all new radiopharmaceuticals for different organ
studies. Chapter 14 is a new chapter titled "Therapeutic Uses of Radio
pharmaceuticals" to highlight different radiopharmaceuticals for therapy.
Adverse reactions and iatrogenic alterations in biodistribution of radio-
vii
viii Preface
pharmaceuticals are included in Chapter 15. Only partial but relevant refer
ences have been included in Chapters 7 and 13.
I am grateful to Dr. Raymundo T. Go, chairman of our department, for
his continued support and understanding.
I would like to express my sincere thanks and appreciation to Ms. Rita
Buzzelli for typing the manuscript very efficiently and conscientiously, and
for timely completion of this edition of the book.
The continued support of the publisher, Springer-Verlag, is greatly
appreciated.
Finally, my wife Sipra's forbearance, encouragement and understanding
made it easier to complete the edition.
Gopal B. Saha
Contents
Preface ................................................................. vii
Chapter 1 The Atom................................................. 1
Electronic Structure of the Atom ................................... 1
Chemical Bonds ..................................................... 3
Electrovalent or Ionic Bond ...................................... 4
Covalent Bond ............................................... . . . . . 5
Coordinate Covalent Bond ....................................... 5
Complex Formation.............................................. 5
Structure of the Nucleus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Nomenclature..................................................... 8
Questions ............................................................ 10
Suggested Reading .................................................. 10
Chapter 2 Radioactive Decay ....................................... 11
Decay of Radionuclides ............................................. 11
Spontaneous Fission .............................................. 11
Alpha (ex) Decay .................................................. 12
Beta (P-) Decay................................................... 12
Positron or (p+) Decay ........................................... 14
Electron Capture (EC) ............................................ 14
Isomeric Transition (IT) .......................................... 15
Radioactive Decay Equations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
General Equation ................................................. 17
Half-Life and Mean Life.......................................... 19
Units of Radioactivity............................................ 20
Calculations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Successive Decay Equations......................................... 22
General Equation ................................................. 22
Transient Equilibrium ............................................ 22
Secular Equilibrium............................................... 24
Statistics of Counting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
ix
x Contents
Error, Accuracy, and Precision................................... 26
Standard Deviation ............................................... 26
Standard Deviation of Count Rates .............................. 27
Propagation of Errors. . .. . . . . . .. . .. . . .. .. . .. . . .. . .. . . . .. . . .. . .. . . . 28
Questions ............................................................ 28
Suggested Reading .................................................. 30
Chapter 3 Instruments for Radiation Detection and Measurement 31
Gas-Filled Detectors ................................................ 31
Dose Calibrators ... . . .. .. . . .. .. . .. . .. . .. .. . . . . . .. . . . . . . . . . . . . . . . . . 31
Geiger-Muller Counters..... . ............... ....... .............. . 33
Scintillation Detecting Instruments ................................. 34
Collimator ........................................................ 34
Detector........................................................... 35
Photomultiplier Tube ............................................. 36
Preamplifier ....................................................... 36
Linear Amplifier .................................................. 36
Pulse Height Analyzer............................................ 37
Display or Storage ................................................ 37
Scintillation Camera. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Collimator ........................................................ 39
Detector. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
X, Y Positioning Circuit .......................................... 40
Pulse Height Analyzer ............................................ 41
Display or Storage................................................ 41
Tomographic Imagers. . . .. . . . . . . . . . . . . . . .. . . . .. . . . . . . . . . . . . . . . . . . . . . 43
Single Photon Emission Computed Tomography ................ 43
Positron Emission Tomography.................................. 44
Questions ............................................................ 45
Suggested Reading .................................................. 46
Chapter 4 Production of Radionuclides ............................. 47
Cyclotron-Produced Radionuclides ................................. 48
Gallium-67 ........................................................ 50
Iodine-123 ......................................................... 50
Indium-Ill........................................................ 51
Thallium-20l ...................................................... 51
Short-Lived Radionuclides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Reactor-Produced Radionuclides ................................... 53
Fission or (n,J) Reaction......................................... 54
Iodine-13l ......................................................... 55
Molybdenum-99 .................................................. 55
Neutron Capture or (n, y) Reaction............................... 55
Target and Its Processing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Contents xi
Equation for Production of Radionuclides . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Specific Activity ..................................................... 60
Questions ............................................................ 63
Suggested Reading .................................................. 63
Chapter 5 Radionuclide Generators................................. 65
Principles of a Generator. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Important Radionuclide Generators ................................ 68
99Mo_99mTc Generator ........................................... 68
I13Sn_113mIn Generator........................................... 76
68Ge_68Ga Generator. '" ................ , ....... .. .. .. ..... . ..... 76
82Sr_82Rb Generator (Cardiogen-82) ............................. 77
62Zn_62Cu Generator. ... ... . ... . . . . . ... . ... . ... .. . ...... . .. .... . . 77
81Rb_81mKr Generator........................................... 77
Questions ............................................................ 77
References and Suggested Reading ................................. 78
Chapter 6 Radiopharmaceuticals and Methods of Radiolabeling . . 80
Definition of a Radiopharmaceutical ............................... 80
Ideal Radiopharmaceutical. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Easy Availability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Short Effective Half-Life.......................................... 81
Particle Emission. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Decay by Electron Capture or Isomeric Transition .............. 82
High Target-to-Nontarget Activity Ratio ........................ 83
Design of New Radiopharmaceuticals .............................. 84
General Considerations ........................................... 84
Factors Influencing the Design of New Radiopharmaceuticals .. 85
Methods of Radiolabeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Isotope Exchange Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Introduction of a Foreign Label.................................. 89
Labeling with Bifunctional Chelating Agents .................... 89
Biosynthesis ....................................................... 90
Recoil Labeling ................................................... 90
Excitation Labeling ............................................... 90
Important Factors in Labeling ...................................... 90
Efficiency of the Labeling Process ................................ 91
Chemical Stability of the Product ................................ 91
Denaturation or Alteration ....................................... 91
Isotope Effect ..................................................... 91
Carrier-Free or No-Carrier-Added (NCA) State................. 91
Storage Conditions................................................ 91
Specific Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
Radiolysis ......................................................... 92
