Fundamentals. Nuclear Pharmacy

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1 Fundamentals of Nuclear Pharmacy

2 Gopal B. Saha Fundamentals of Nuclear Pharmacy With 88 illustrations IS] Springer Science+Business Media, LLC

3 Gopal B. Saha, Ph.D. Associate Professor of Radiology (Nuclear Medicine) and Pharmacy Director of Radiopharmaceutical Program (Nuclear Medicine) University of Arkansas for Medical Sciences Little Rock, Arkansas 72201/U.S.A. Library of Congress Cataloging in Publication Data Saha, Gopal B Fundamentals of nuclear pharmacy. Includes bibliographies and index. 1. Radiopharmaceuticals. I. Title. RM852.S23 615' All rights reserved. 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 by Springer Science+Business Media New York Originally published by Springer-Verlag New York Inc. in Softcover reprint of the hardcover 1 st edition ISBN DOI / ISBN (ebook)

4 To my wife, Sipra and my children, Prantik and Trina

5 Foreword Nuclear medicine is an ever changing subject, and the emphasis and utility of one type of study is often abruptly supplanted by another. In this unstable environment, there is a set of circumstances that offers a basic unifying structure to the activities encountered in nuclear medicine. The pivotal importance of radio pharmaceuticals in these activities makes a thorough understanding of them paramount for all who would prescribe, dispense, or in any way utilize such materials. In this volume, the author has distilled an awesome body of literature on nuclear pharmacy into a concise and readily understandable textbook. It is written from the viewpoint of one who not only has broad experience and knowledge in nuclear pharmacy, who daily guides and instructs a variety of students in the discipline, but who also directs a clinical nuclear medicine radiopharmacy program. In this book he has avoided the esoteric and maintained an emphasis on the practical. The approach is not encyclopedic in nature, as adequate references refer the more interested reader to appropriate sources of detailed information, but one which ensures that the students will be able to absorb the essentials of nuclear pharmacy and practice it effectively with a broad understanding of the subject. At the end of each chapter a set of questions provokes the reader to assess the sufficiency of the knowledge gained. Since nuclear pharmacy has become an essential central element of the nuclear medicine laboratory and involves a wide variety of participants, use of this book will undoubtedly benefit the practice of nuclear medicine generally and the patient specifically. Charles M. Boyd, M.D. Professor and Head, Division of Nuclear Medicine University of Arkansas for Medical Sciences Little Rock, Arkansas

6 Preface With the vast expansion of nuclear medicine, the discipline of radio pharmacy has grown extensively, and it is now considered a separate unit in many nuclear medicine facilities. Many centralized radiopharmacies have been established to supply radiopharmaceuticals to more than one hospital. In view of this great appreciation of radiopharmacy, many schools of pharmacy and nuclear medicine technology are instituting training programs and are offering courses in nuclear pharmacy. Obviously, a book to meet these teaching demands is definitely needed. This book is a result of my courses offered to pharmacy students specializing in nuclear pharmacy, to nuclear medicine residents, and to nuclear medicine technology students at the University of Arkansas for Medical Sciences. The topics included are comprehensive, ranging from the basic concept of atomic structure to practical clinical uses of radio pharmaceuticals, but coverage is concise, limited greatly to the preparation, quality control, dispensing, and disposal of radiopharmaceuticals. Concise reviews of pertinent basic science information and a list of suggested readings at the end of each chapter make this an ideal textbook of nuclear pharmacy. The liberal use of tables and the appendixes facilitate the concise inclusion of much data and make the book a very useful reference for many nuclear medicine professionals, such as physicians, residents, and technologists. The book contains twelve chapters. The subject of each is covered as comprehensively as possible, based on my personal experience and understanding and in keeping with the design of the book. At the end of each chapter, I have included a section of pertinent questions and problems. Chapter I briefly reviews atomic structure, electron configuration of atoms, chemical bonds, and nuclear structure. The chapter is primarily designed to provide an understanding of chemical bonds and nuclear structure and to acquaint the reader with different nomenclatures associated with nuclei of varying composition. ix

7 x Preface The different decay modes of radionuclides and various mathematical equations related to them are discussed in Chapter 2. A section is devoted to statistics of counting. A description of the general methods of production of radionuclides in cyclotrons and reactors is given in Chapter 3. In Chapter 4 the principles of a radionuclide generator are elaborated. A detailed description of a 99Mo-99mTc generator is presented along with quality control measures that are essential for this generator. In Chapter 5 the term radiopharmaceutical is defined and the ideal characteristics of a radiopharmaceutical and various dosage forms in which it may be dispensed are described. Information about how to design a new radiopharmaceutical is also provided in this chapter. Chapter 6 is a review of the general principles of labeling of compounds with special reference to various factors that affect labeling. The methods of iodination and 99mTc-labeling are described in detail. There is also a brief review of different additives used in radiopharmaceuticals. In Chapter 7 the general features of the preparations are presented and various characteristics of specific radio pharmaceuticals that are routinely used in nuclear medicine are discussed. Various physicochemical factors affecting the yield and stability of the labeled compounds are presented for ready reference when problems associated with any radiopharmaceutical arise. In Chapter 8 the reader is introduced to various quality control tests of radiopharmaceuticals that must be carried out before administration to humans. In Chapter 9 a description of a radiopharmacy set-up is given with regard to its design and the daily procedures of preparation, quality control tests, and dispensing of radiopharmaceuticals. Chapter 10 is a discussion of the general aspects of radiation dosimetry, safety, and federal and state regulations governing the use of radiopharmaceuticals. The general principles of radioimmunoassay and brief methods of some pertinent in vitro tests are presented in Chapter 11. Chapter 12 is concerned with the subject of radiopharmacology in nuclear medicine. This chapter is divided into sections on each organ to be imaged. At the beginning of each section a brief description of the anatomy and physiology of the organ in question is presented, and then the various radio pharmaceuticals and the imaging techniques used in that organ are discussed. The mechanism of localization and the biologic handling of each radiopharmaceutical is elucidated wherever possible. A brief section is devoted to radionuclide therapy. Several appendixes have been included that list useful data such as universal constants, decay factors of 99mTc and 131 1, and answers to the mathematical problems given at the end of various chapters. A glossary and a list of abbreviations used in the text have also been included in the appendixes.

8 Preface xi I do not pretend to be infallible in writing a book of such diversified scientific information. Many errors of both commission and omission may have occurred, and I would appreciate having them brought to my attention by the interested readers. It would have been impossible to complete this book without the help and suggestions of many people. First and foremost, I am ever grateful to Dr. Claude E. Epperson of the College of Pharmacy at the University of Arkansas for Medical Sciences, Little Rock, whose perusal of the entire manuscript, helpful criticism, invaluable suggestions, and friendly encouragement made this book possible. Special gratitude is extended to Or. Charles M. Boyd of the University of Arkansas for Medical Sciences, to whom I owe a great deal for his continued support and understanding. I extend my sincere thanks to Dr. M. K. Dewanjee of the Mayo Clinic and Mayo Foundation, Rochester, Minnesota, J. F. Vandergrift of the University of Arkansas for Medical Sciences, Or. P. A. Farrer of the University of California at Davis, and Dr. F. Vieras of the Armed Forces Radiobiology Research Institute, Bethesda, Maryland, for suggestions and comments on various chapters of the book. Thanks are due Alice Guy Anne Ransom for her help in sorting out the suitable scans and scintiphotographs, and Susan Hudgens, Michael A. Morris, and others of Biomedical Communications at the University of Arkansas for Medical Sciences for their assistance in the illustrations and photographic work. The cooperation and assistance in numerous ways of the members of the Division of Nuclear Medicine at the University of Arkansas for Medical Sciences is greatly appreciated. Appreciation is also due the publisher, Springer-Verlag, for its full cooperation toward the project. I would like to express my heartfelt gratitude to Vercie Vandergrift, who typed the manuscript over and over so graciously, conscientiously, and efficiently, and whose tireless and painstaking effort played an instrumental role in bringing this book to fruition. Finally, my wife Sipra's inspiration, encouragement, and forbearance throughout this endeavor made my work a pleasure. Gopal B. Saha

9 Contents Chapter 1 The Atom Electronic Structure of the Atom 1 Chemical Bonds 4 Structure of the Nucleus 8 Chapter 2 Radioactive Decay 13 Decay of Radionuclides 13 Radioactive Decay Equations 19 Successive Decay Equations 24 Statistics of Counting 28 Chapter 3 Production of Radionuclides 33 Cyclotron-Produced Radionuclides 34 Reactor-Produced Radionuclides 37 Target and Its Processing 40 Equation for Production of Radionuclides 41 Specific Activity 47 Chapter 4 Radionuclide Generators 51 Principles of a Generator 51 Important Radionuclide Generators 54 Chapter 5 Radiopharmaceuticals 65 Ideal Radiopharmaceutical 67 Dosage Forms 71 Design of New Radiopharmaceuticals 71 Chapter 6 Radiolabeling of Compounds 79 Methods of Labeling 79 Important Factors in Labeling 82 xiii

10 xiv Contents Specific Methods of Labeling 84 Colloids and Labeled Particles 91 Additives 92 Chapter 7 Characteristics of Specific Radiopharmaceuticals 95 99mTc-Labeled Compounds 95 Radioiodinated Compounds 104 Miscellaneous Compounds of Clinical Interest 109 Chapter 8 Quality Control of Radiopharmaceuticals 117 Physicochemical Tests 118 Biologic Tests 134 Record Keeping 139 Chapter 9 Radiopharmacy 143 Concept 143 Design of a Radiopharmacy Operation of a Radiopharmacy Centralized Radiopharmacy Chapter 10 Radiation Dosimetry, Safety, and Regulations 155 Radiation Dosimetry 155 Radiation Safety 160 Radiation Regulations 170 Chapter 11 In Vitro Tests 175 Radioimmunoassay 175 Schilling Test 179 Blood Volume 179 Red Blood Cell Survival 181 Plasma Iron Clearance and Turnover Rate 182 Chapter 12 Radiopharmacology in Nuclear Medicine 185 Central Nervous System 185 Thyroid 192 Lung 198 Liver 205 Spleen 212 Pancreas 213 Kidney 215 Skeleton 224 Bone Marrow 228 Heart 230 Miscellaneous Imaging Radionuclide Therapy

11 Contents xv Appendix A Abbreviations Used in Text 247 Appendix B Terms Used in Text 249 Appendix C Units and Constants 255 Appendix D Radioactive Decay of 99mTc 257 Appendix E Radioactive Decay of Appendix F Generic Names, Brand Names, and Suppliers of Kits 261 Appendix G Answers to Questions 263 Index 265

METHODS FOR PROTEIN ANALYSIS

METHODS FOR PROTEIN ANALYSIS Robert A. Copeland, PhD The DuPont Merck Pharmaceutical Company Experimental Station P.O. Box 80400 Wilmington, DE 19880-0400 METHODS FOR PROTEIN ANALYSIS A Practical Guide