. ."
`
`."
`
`Essentials of
`NUCLEAR MEDICINE
`SCIENCE
`
`. . . .. ..
`
`. ." .
`
`MAIA Exhibit 1030
`MAIA V. BRACCO
`IPR PETITION
`
`

`

`Essentials of
`NUCLEAR MEDICINE
`SCIENCE
`
`Edited by
`William B . Hladik 111, M.S., R . Ph.
`Associate Professor of Pharmacy and Director of Radiopharmacy
`College of Pharmacy
`University of New )Mexico
`Albuquerque, New Mexico
`Gopal B . Saha, Ph.D.
`Staff Radiochemist
`Department of Nuclear Medicine
`The Cleveland Clinic Foundation
`Cleveland, Ohio
`
`Kenneth T. Study, B.S. , C.N.M. T.
`
`Medical Accounts Manager
`Digital Equipment Corporalion
`Albuquerque, New Mexico
`
`With the technical assistance of
`Blair E . Friedman, M.A.
`Senior Technical Sales Representative
`Medi-Physics, Inc.
`Lake Worth, Florida
`
`WILLIAMS & WlLKlNS
`Balllmore London Los Angeles Sydney
`
`I
`1
`
`

`

`Edimr: John Butler
`Associare Ediror: Victoria M. Vaughn
`Copy Ediror: Bill Cady
`Design: Bob Och
`illusrrarion Plalmirlg: Lorraine Wrzosek
`Prodrdorz: Raymond E. Rcler
`
`Copyright 0 I987
`JVi\liams & Wilkins
`428 East Preston Street
`BaItimore, MD 21202, U . S . A .
`
`copyright. No part oi this book may be
`This book is protected by
`All rights reserved
`or utilued by any
`reproduced in any form or by any ~nenns. Including pholocopying,
`mformatlon storage and retrieval system without written permission from the copyright owner
`
`for drugs arc provided in this
`Accurm indicatlons. adverse reactions, and dosage scheduIes
`they may change. The reader is urged to review the package
`book, but it is possible that
`information data of the manufacturers of the medications mentioned
`
`Prirmd irl Ihe Uniied Slam of America
`
`Library of Congress Cataloging-in-Publication Data
`
`Main entry under title:
`
`Essentials of nuclear medicine science.
`
`index.
`Includes bibliographies and
`B.. 195G
`1. Radiopharmaceuricals. 2. Nuclear medicine. 1. Hladik. William
`, 11.
`Saha. Gopal 8. III. Study, Kenncth T. [DNLM: 1. Nuclcar Medicine. WN 440 E781
`I987
`
`616.07'57 8517978
`R M 852.E87
`ISBN 0-683-04051-0
`
`Printed at the
`Waverly Press. Inc
`
`87 88 89 90 91
`1 0 9 8 7 6 5 4 3 2 1
`
`To our wives:
`
`Leslie
`Sipra
`Linda
`
`and our children:
`
`Billy and Anya
`Pranlik and Trina
`Jessica
`
`without whose love,
`encouragement and patience
`this project would
`have never been completed
`
`

`

`Foreword
`
`Science in the service of the clinical practice of nuclear medicine often utilizes a variety
`of a radioactive tracer
`of problem-solving techniques. The biodistribution
`can provide
`significant physiologic, biochemical, and anatomic information regarding the health status
`of a patient. However, many parameters can influence the biodistribution of a radiotracer
`and confound the diagnostic information. In addition to the intrinsic biological factors that
`determine the basic distribution pattern, there are extrinsic factors (e.g., procedural errors,
`instrumentation errors, and adverse reactions) which can influence the presentation of the
`of the study. By knowing what these potential
`data and, thus, the ultimate outcome
`confounding factors are and how they operate, tough diagnostic questions can often be
`resolved.
`When examining an individual study, we are often faced with the problem of differ-
`entiating what is unique from what is a repeated pattern. As more experience is gained, the
`once unique event becomes a known and repeated, but often rare, pattern. The sharing of
`is a powerful way to
`information from various branches of nuclear medicine science
`improve our skills
`in dealing with these day-to-day unusual patterns. In turn, the diag-
`is improved. The
`objective of collecting and
`nostic potential
`of radiotracer studies
`organizing the idormation which helps us to recognize and understand the quirks of tracer
`biodistribufons (and external variables which influence
`data capture) has been a major
`preparation of this volume. The various
`undertaking-an
`undertaking essential to the
`authors have done well to provide the reader with this collection of data and its synthesis
`into a basic reference.
`1977, the
`The task which culminates with this book was started many years ago. In
`faculty and staff of the University of New Mexico (UNM) Radiopharmacy realized that
`there was a critical need to teach radiopharmacy students the clinical side of their specialty
`practice more effectively. The effort to achieve
`a more clinically oriented
`teaching
`program required that data be collected from the various scientific specialists who serve on
`to students and
`nuclear medical teams. As the information grew and was passed on
`associates in the field, its value became increasingly apparent. This information has been
`shared via informal telephone exchange for a number of years. What the staff of the UNM
`Radiopharmacy was doing was also being done by other professionals at various nuclear
`medicine institutions. In time, it be.came more and more evident that there was a real need
`to compile the information that was being networked into a reference book. A number of
`authors have combined their efforts and information into a collection of manuscripts which
`will serve well those who are faced with the task of interpreting biodistribution studies-
`studies which may have been influenced by possible, and sometimes rare, confounding
`parameters.
`
`Buck A. Rhodes, Ph.D.
`Albuquerque, New Mexico
`
`1
`
`!
`
`

`

`Preface
`
`The nuclear medicine physician, in arriving at a diagnostic conclusion, uses multiple
`sources of information, UsuaIly the data (images or numerical values) are evaluated, de
`novo, as
`the primary source of infomation to insure
`that the initial impressions are
`This may include: (a) comments
`unbiased. Next, the anciilary information is obtained.
`from the referring physician and other information regarding the patient, (b) procedural
`information supplied by the technology staff, (c) data from physicists, computer spe-
`who may have had involvement in the
`cialists, or other nuclear medicine scientists
`procedure, and (d) pharmaceutical information from the staff responsible for preparing the
`radioactive Lracer drugs. The physician’s interpretation results from an integration of these
`primary and ancillary information sources plus knowledge gained from previous training
`and experience.
`This book provides the reader with a wide scope of ancillary information on radiophar-
`maceuticah (and related subjects) that can be used to strengthen both the nuclear medicine
`clinical decision-making process as well as the radiopharmaceutical evaluation process. In
`in the secondary literature
`general, chapter topics compensate for current deficiencies
`relative to radiopharmaceuticals and other technological and biological parameters that
`must be taken into consideration by nuclear medicine professionals in their daily practice.
`The format of this book is such that physicians, pharmacists, Lechnologists, and other
`scientists in the specialty area of nuclear medicine can utilize it as a textbook when they
`are students and then as a reference volume when they are carrying out their respective
`clinical functions.
`specialties,
`than most other medical
`that nuclear medicine, more
`It seems apparent
`brings together quite a variety of scientists and professionals. Depending on the mix of
`scientists in a particular department, any one individual may take on a variable number of
`clinical responsibilities and thus must be familiar with a broad scope of topics beyond his
`or her specific area of expertise. Chapters in this book are intended to supply information
`which will assist nuclear medicine professionals with varied backgrounds and strengths to
`become more active and competent consultants in the clinical setting. Even with this in
`mind, this book is certainly not all-inclusive; rather, it touches on those areas about which
`the professional is frequently called upon to act as a source of information.
`The use of the word “essentials” in the title of this book should not be construed to
`mean “basics.” We assume that those who use this book will already be well trained in Lhe
`basic concepts of their primary discipline related to nuclear medicine, i.e., health physics,
`technology, chemistry, pharmacy, medicine, etc., and thus there is no need to include such
`information in this book. However, all of lhe material herein is essential if he individual is
`to communicate effectively and serve as a source of current and relevant information.
`The stimulus for the development of this book was primarily forthcoming from inqui-
`ries directed to the University of New Mexico (UNM) Radiopharmacy. The UNM group
`has operated a consultation service for local, state, and national callers seeking answers to
`
`

`

`questions or problems ~ I
`lhry t w cncountering in nuclear medicine, particularly specific
`
`I
`and detailed information pcrhining to physical, pharmacologic, physiologic, pharmacoki-
`netic, or quality CO~IIIUI p;ll’;llncters which influence the in vivo performance of radioactive
`tracers. This 11;~s providcrl 11s with the opportunity to collect and organize the data into a
`bank of rcxlily ~r~ricv;~ble
`information, which served as
`the nucleus €or the book.
`Aulhrrs (11 tach chapter were selected on the basis of their individual expertise in the
`as
`p;u.ticul;u a ~ a . Chapters have been written
`
`with as much up-to-date information
`possihlc and are adequately referenced. Because each chapter
`is written by different
`there is some
`inadvertent overlap of contents in different
`:luthors on related matter,
`chapters despite our careful editing. Due io the rapid pace of nuclear medicine growth and
`the long procress of editing and publishing, certain recentIy released information couid not
`be included in the book.
`
`William B. HIadik 111
`Gopal B. Saha
`Kenneth T. Study
`
`Acknowledgments
`
`The editors would like to thank particularly Buck A. Rhodes, Ph.D., who suggested the
`need for this type of book and helped to
`develop its “character.” His foresight and
`inspiration are deeply appreciated.
`We are indebted to Blair E. Friedman, M.A., who was
`instrumental in contacting
`potential authors, making arrangements with the publisher, and proofreading the typeset
`COPY.
`We would also like to acknowledge Kay L. Hicks, Elva G. Giron, Sharon 1. Ramirez,
`and Jennifer A. Farenbaugh for their supxb secretarial assistance.
`For her photography expertise, we acknowledge and thank Chris Martin, Albuquerque,
`New Mexico, who supplied the iamge ultimately selected for the book cover.
`Our sincerest thanks go to Zophia Pastuszyn, C.N.M.T., Ruth Snyder, and the entire
`staff in the nuclear medicine department
`at Lovelace Medical Center, for providing
`scintiscans considered for the book cover.
`Special credit is extended to the staff of Williams & Wilkins for their advice and
`patience during the development and production of this book.
`We gratefully acknowledge Carnlan A . Bliss, Dean of the College of Pharmacy,
`University of New Mexico, and the management of Digital Equipment Corporation for
`their support of this task.
`to the contributors who have
`deepest appreciation
`Finally, the editors
`extend their
`cooperated fully in ali aspects of the preparation of this text.
`
`xi
`
`

`

`Contributors
`
`Neil Abel, M.S., M.B.A.
`Reviewing Pharmacist
`Food and Drug Administration
`Rockville, MaryIand
`
`Harold L. Atkins, M.D.
`Professor of Radiology
`School of Medicine
`Health Sciences Center
`Stale University of New York at Stony BI
`.oak
`Stony Brook, New York
`and
`Chief, Division of Nuclear Medicine
`Department of Radiology
`University Hospital at Stony Brook
`Stony Brook, New York
`
`William J. Baker, M.S.
`Associate Professor of Nuclear Pharmacy and
`Director, Intermountain Radiopharmacy
`College of Pharmacy
`University of Utah Health Sciences Center
`Salt Lake City, Ulah
`
`Robert W. Beightol, Pharm.D., B.C.N.P.
`Director, Nuclear Pharmacy Senices
`Roanoke Memorial Hospitak
`Roanoke, Virginia
`
`Ralph Blumhardt, M.D.
`Associate Professor of Radiology and
`Head of Division of Nuclear Medicine
`University of Texas Health Science Center at San
`Antonio
`San Antonio, Texas
`
`Terry L. Braun, B.S., R.Ph.
`Radiochemisl
`Cancer Therapy Inslitute
`King hisal Specialist Hospital
`Riyadh, Saudia Arabia
`
`Donald A. Bille, Ph.D., R.N.
`Nursing School Professor
`Graduate Faculty
`Graduale Department of Nursing Education,
`Administration, and Heallh Policy
`School of Nursing
`University of Maryland
`Baltimore, Maryland
`Doyle W, Canfrell, B.A., R.T.(N), C.N.M.T.
`Director of Medical Imaging
`Park Lane Medical Cenler
`Kansas City, Missouri
`Teresa J. Cantrell, B.A., R.T.(N), C.N.M.T.
`Supervisor of Nuclear Medicine/Ullrasound
`Department of Radiology
`St. Luke5 Hospital
`Kansas Cily, Missouri
`Henry M. Chilton, PharmD.
`Associate Professor
`Division of Nuclear Medicine
`Department of Radiology
`Bowman Gray School of Medicine
`Wake Forest University
`Winston-Salem, North Carolina
`Jeffrey A. Clanton, M.S., B.C.N.P.
`Associate in Radiology and
`Chief of Radiopharmacy Services
`Vanderbilt University Medical Center
`Nashville, Tennessee
`Jack L. Coney, M.S., C.H.P.
`Health Physicist
`Syncor International Corporation
`Albuquerque, New Mexico
`Larry T. Cook, Ph.D.
`Associate Professor of Diagnostic Radiology
`Division of Diagnostic Imaging and Radiological
`Science
`Department of Diagnostic Radiology
`University of Kansas Medical Center
`Kansas City, Kansas
`xiii
`
`

`

`xiv
`
`t Contributors
`
`M. Annette Cordova, M S . , R.Ph.
`Assistanl Director
`Department of Pharmacy
`Northeast Community Hospital
`Sedford, Texas
`
`John J. Coupal, Ph.D.
`Assistant Clinical Professor of Radiation Medicine
`
`
`
`College of Medicine Hermann Hospital
`
`
`
`
`
`Universitv of Kentuckv Houston, Texas
`Lexington, Kentucky
`and
`Nuclear Pharmacist
`Nuclear Medicine Service
`Veterans Administration Medical Center
`Lexington, Kentucky
`
`Robert J. Cowan, M.D.
`Professor of RadioIogy
`Division of Nuclear Medicine
`Department of Radiology
`Bowman Gray School of Medicine
`Wake Forest University
`Winston-Salem, North Carolina
`
`Frederick L. Datz, M.D.
`Associate Professor of Radiology and
`Clinical Director of Nuclear Medicine
`School of Medicine
`University of Utah Health Sciences Center William B.
`
`
`
`
`
` Utah Salt Lake City, Associate Professor
`
`
`
`
`
`Natalie Foster, Ph.D.
`Assistant Professor
`Department of Chemistry
`Center for Health Sciences
`Lehigh University
`BethIehem, Pennsylvania
`and
`Adjunct Assistant Professor
`Department of Radiation Oncology and Nuclear
`Medicine
`Hahnemann University
`PhiladeIphia, Pennsyivania
`
`John E. Freilas, M.D.
`Nuclear Medicine Deparhent
`William Beaumont Hospital
`Royal Oak, Michigan
`and
`Clinical Associate Professor
`University of Michigan Medical SchooI
`Ann Arbor, Michigan
`and
`Clinical Associate Professor
`School of Medicine
`Wayne State University
`Detroit, Michigan
`
`Allan H. Gobuty, Pharm,D., M.S.
`Assistant Professor of Radiology
`Medical School
`University of Texas Health Science Center at
`Houston
`Houston, Texas
`and
`
`Ned Gregorio, R.Ph., B.C.N.P.
`Nuclear Pharmacist
`Radiopharmacy
`College of Pharmacy
`University of New Mexico
`Albuquerque, New Mexico
`
`Ned D. Heindel, Ph.D.
`Professor, Department of Chemistry and
`Director, Center for Health Sciences
`Lehigh University
`Bethlehem, Pennsylvania
`and
`Adjunct Professor
`Department of Radiation Oncology and Nuclear
`Medicine
`Hahnemann University
`Philadelphia, Pennsylvania
`
`Hladik 111, M S . , R.Ph.
`
`of Pharmacy and
`
`Director of Radiopharmacy
`College of Pharmacy
`University of New Mexico
`Albuquerque, New Mexico
`
`Robert Hodges, PharmD.
`Staff Pharmacist
`Washington Regional Medical Center
`Fayetteville, Arkansas
`
`Karl F. Hubner, M.D.
`Professor of Radiology and
`Director of Research
`Department of Radiology
`University of Tennessee Hospital
`Knoxville. Tennessee
`
`Xobert C. Jost, M.S., R.Ph.
`Pharmacist
`University of New Mexico Hospital
`Albuquerque, New Mexico
`
`E. Edmund Kim, M.D., M.S.
`Professor of Radiology and Medicine, and
`Direclor, Division of Nuclear Medicine
`University of Texas Health Science Center at
`Houston
`Houston, Texas
`
`Jack L. Lancaster, Ph.D.
`Assistant Professor of Radiology and
`Head of Diagnostic Radiology Physics Section
`University of Texas Health Science Center at San
`Antonio
`San Antonio, Texas
`
`John C. Lasher, M.D.
`Assistant Professor of Radiology
`University of Texas Health Science Center at San
`Antonio
`San Antonio, Texas
`
`David L. Laven, C.R.Ph. F.A.S.C.P.
`Director, Nuclear Pharmacy Service
`Nuclear Medicine Department
`Veterans Administration Medical Center
`Bay Pines, Fbrida
`
`Brian C. Lentle, M.D., F.R.C.P.(C)
`Director, Departmenl of Nuclear Medicine
`Vancouver General Hospilal
`Vancouver, British CoIumbia
`and
`Head, Division of Nuclear Medicine
`Department of Radiology
`University of British Columbia
`Vancouver. British Columbia
`
`Geoffrey Levine, Ph.D., B.C.N.P.
`Associate Professor of Radiology
`School of Medicine
`University of Pittsburgh
`Pittsburgh, Pennsylvania
`and
`Clinical Associate Professor of Pharmaceutical
`Sciences
`School of Pharmacy
`University of Pittsburgh
`Pittsburgh, Pennsylvania
`and
`Director of Nuclear Pharmacy
`Presbyterian-University Hospital
`Pittsburgh, Pennsylvania
`Zvi €I. Oster, M.D.
`Professor o€ Radiology
`School of Medicine
`Health Sciences Center
`State University o€ New York at Stony Brook
`Stony Brook, New York
`and
`Co-Chief, Division of Nuclear Medicine
`Department of Radiology
`University Hospital at Stony Brook
`Stony Brook, New York
`and
`Research Collaborator and
`Visiting Clinician
`Medical Deparlmenl
`
`Brookhaven NationaI Laboratory
`Upton, New York
`James A. Ponto, M.S., R.Ph., B.C.N.P.
`Nuclear Pharmacist
`Department of Radiology
`University of Iowa Hospitals and Clinics
`Iowa City, Iowa
`and
`ClinicaI Associate Professor
`College of Pharmacy
`University of Iowa
`Iowa City, Iowa
`David F. Preston, M.D.
`F’rofessor of Diagnostic Radiology
`Division of Nuclear Medicine
`Departrnenl of Diagnostic Radiology
`University of Kansas Medical CenteI
`Kansas City, Kansas
`Bock A. Rhodes, PhD.
`President
`RhoMed, Inc.
`Albuquerque, New Mexico
`Gopal B. Saha, Ph.D.
`Staff Radiochemist
`Department of Nuclear Medicine
`The Cleveland Clinic Foundation
`Cleveland, Ohio
`Pranlika Som, D.V.M., Sc.M.
`Scientist
`Brookhaven Nalional Laboratory
`Uplon, New York
`and
`Research Associate Professor of Radiology
`School of Medicine
`HeaIth Sciences Center
`State University of New York at Stony Brook
`Stony Brook, New York
`
`Michael G. Stabin, M.E.
`Radiopharmaceutical Internal Dose Information
`Cenler
`Manpower Education, Research and Training
`Division
`Oak Ridge Associated Universities
`Oak Ridge, Tennessee
`Victor J. Slathis, B.S., R.Ph.
`Nuclear Pharmacist
`Pharmacy Department
`N. T. Enloe Memorial Hospital
`Chico, California
`Kenneth T. Study, B.S., C.N.M.T.
`Medical Accounts Manager
`Digital Equipment Corporation
`Albuquerque, New Mexico
`
`

`

`xvi
`
`I Contributors
`
`Colin B. Styles, M.D.
`Department of Nuclear Medicine
`St. Vincent’s Hospital
`Victoria Parade
`Fitzroy 3065, Australia
`
`Dennis P. Swanson, MS., R.Ph., B.C.N.P.
`Department of Diagnoslic Radiology and Medical
`Imaging
`Henry Ford HospitaI
`Detroit, Michigan
`and
`Clinical Associate Professor of Pharmacy
`College of Pharmacy
`University of Michigan
`AM Arbor, Michigan
`and
`Adjunct Associate Professor of Pharmacy Practice
`SchooI of Pharmacy
`Wayne State University
`Detroit, Michigan
`
`Roger W. TaR, B.S., C.N.M.T.
`Section Supervisor
`Division of Nuclear Medicine
`Department of Radiology
`Heights General Hospital
`Albuquerque, New Mexico
`James E Vandergrift, M.S.
`Assistant Professor of Radiology (Physics) and
`Radiation Safety Officer
`College of Medicine
`University of Arkansas for Medical Sciences
`Little Rock, Arkansas
`Evelyn E. Watson
`Program Manager
`RadiopharmaceuticaI Internal Dose Information
`Center
`Manpower Education, Research and Training
`Division
`Oak Ridge Associated Universities
`Oak Ridge, Tennessee
`
`Contents
`
`Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Preface
`
`ix
`Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`I
`Considerations for the Clinical Use
`of Radiopharmaceuticals
`
`Chapter 1
`Normal Biodistribution of Diagnostic Radiopharmaceuticals
`Go~nlB.Srrha . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 2
`Radiopharmacokinetics in Nuclear Medicine
`J e f f r e y A . C l a n t o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 3
`Biodistribution and Structure in Radiodiagnostics
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Ned D . Heildei m d Natalie Foster
`Chapter 4
`Metabolic Fate of Radiopharmaceuticals
`R o b e r i C . J o s i . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 5
`Radiopharmaceutical Absorbed Dose Consideralions
`Jack L. Coffeer, Evelyn E. Watson, Karl F. Hubrrer, arrd Michael G . Stabin . .
`Chapter 6
`of Radiopharmaceuticals
`Considerations and Controversies in the Selection
`Henry M . Chilton and Robert J. ConIan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 7
`Therapeutic Applications of Radiopharmaceuticals
`William J. Baker, Frederick L. Dalz, and Robert W. Beightol
`Chapter 8
`Preparation and Clinical Utility of Labeled Blood Products
`Willirrm J. Baker and Frederick L. Dalz . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 9
`Nuclear Medicine Procedures for Monitoring Patient Therapy
`Alla?~ H . Goblrty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`I
`
`vii
`
`xi
`...
`x111
`
`3
`
`20
`
`33
`
`44
`
`. 51
`
`75
`
`x4
`
`90
`
`99
`
`

`

`Chapter 21
`Regulatory Problems in Nuclear Medicine
`James F. Vandergrifl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`III
`Considerations for the Preclinical and the Clinical Investigation
`of New Radiopharmaceuticals
`
`Chapter 22
`Animal Models of Human Disease
`Prantika Son1 and Zvi H . Oster . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 23
`Considerations in the Assembly and Submission of the Physician-sponsored
`Investigational New Drug Application
`Geoffrey Levine and Neil Abel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`IV
`Interactions among Nuclear Medicine
`Health Care Professionals and Patients
`
`32 1
`
`333
`
`357
`
`Chapter 24
`Radiopharmaceutical Information and Consultation Services
`William B. Hladik iii, Ned Gregorio, Terry L. Bram, Victor J. Stathis, and
`JamesA.Ponto . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 25
`Issues of Patient Education
`Donald A . Bilk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 26
`Patient Preparation for Nuclear Medicine Studies
`Victor J. Stathis, Doyle W. Canrrell, and Teresa J. Cantre11 . . . . . . . . . . . . . . . . 411
`
`404
`
`389
`
`Index
`
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`421
`
`Chapter 10
`Interventional Studies in Nuclear Medicine
`Gopal B . Saha, Dennis P. Swar~son, and William B. Hladik III . . . . . . . . . . . . . 11 5
`Chapter 11
`Medical Decision Making
`David F. Preston and Larry T. Cook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 12
`Computer Applications in Nuclear Medicine
`Jack L. Larrcaster, John C . Lasher, and Ralph Bllrrnhardr . . . . . . . . . . . . . . . . . . 145
`I1
`Problems and Pitfalls Encountered
`with the Use of Radiopharmaceuticals
`
`133
`
`165
`
`Chapter 13
`Iatrogenic Alterations in the Biodistribution of Radiotracers as a R e d of Drug
`Therapy: Theoretical Considerations
`RobertHodges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 14
`Iatrogenic Alterations in the Biodiswibulion of Radiotracers as a ResuIt of Drug
`Therapy: Reported Instances
`William B. Hlodik lli, James A . Ponfo, Brian C. Lentle,
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`and David L. Laven
`Chapler 15
`Iatrogenic Alterations in the Biodistribution of Radiotracers as a Result of
`Radiation Therapy, Surgery, and Other Invasive Medical Procedures
`Brian C . Lenfle and Colin B. SijJles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 16
`Normal Clinical Variation in Anatomic Structure and Physiologic Function and Its
`Effect on Radiopharmaceutical Biodistribution
`John J, Coupal and E. Edn~und Kim . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 17
`Unusual or Unanticipated Alterations in the Biodistribution of
`Radiopharmaceuticals as a Result of Pathologic Mechanisms
`E. Edtnrcnd Kin? arzd John J. Coupal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`Chapter 18
`Clinical Manifestations of Radiopharmaceutical Formulation Problems
`James A. Ponto, Demis P. Swanson, ami John E. Freilas . . . . . . . . . . . . . . . . . . 268
`Chapter 19
`Instrumentation and Procedural Problems in Nuclear Medicine
`Kenneth T, Study and Roger W. Taff . . . . . . . . . . . . . . . . . .
`Chapter 20
`Adverse Reactions Associated with Radiophannaceulicals
`M . Annette Cordovn, William B. Hladik i i I , Brrck A . Rhodes, and
`HaroidL.Atkim . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`189
`
`220
`
`234
`
`248
`
`290
`
`303
`
`

`

`I
`
`Considerations
`for the Clinical Use of
`Radiopharmaceuticals
`
`

`

`1
`Normal Biodistribution of Diagnostic
`Radiopharmaceuticak
`
`generalors with isotonic saline. Sodium
`a diagnostic modality
`Nuclear medicine as
`has grown to such an extent that it is practiced in
`[99mTc]pertechnetate and many 9 9 m T ~ products
`account for almost 80% of the radiopharmaceu-
`almosl all hospitals nationwide. In the practice
`ticals used in nuclear medicine procedures. The
`of nuclear medicine: physicians set norms for
`reason for such a preeminent position for 9 9 m T ~
`morphology or physiologic function of each
`is that its electron emission is
`negligible and
`organ by studying a large number of normal
`thus the radiation dose to patients is minimal.
`palienls. For every procedure, there
`is in these
`of 140 keV is suitable for
`diagnostic data a range of normal variations that
`The y-ray energy
`scintigraphy with a gamma camera.
`are familiar to the physicians. Nuclear medicine
`After intravenous administration, 99mTc-per-
`practitioners interpret
`diseases or pathologies
`technetate* initially distributes itself in the vas-
`that are attributed on the basis of the deviations
`cular compartment. Radiopertechnetate most
`from the limits of these variations.
`closely resembles iodide
`in biologic behavior
`this book pri-
`As indicated in the Preface,
`and becomes plasma protein bound, mostly to
`in the
`marily focuses on ancillary information
`albumin (1). Plasma clearance
`interpretation of nuclear medicine studies. Be-
`is very rapid,
`and equilibrium between vascular compartment
`fore learning about abnormalities along
`with
`and interstitial fluid is achieved in as short a
`various pitfalls and artifacts in a nudear medi-
`time as 2 to 3 minutes. The plasma clearance
`cine study, however, one ought to be familiar
`half-time is approximately 30 minutes. Approx-
`with the normal biodistribution of different ra-
`imately 30% of the administered
`dose is ex-
`diopharmaceuticals. This chapter highlights the
`creted in the first 24 hours. The total urinary
`expected normal biodistributions of various rou-
`and fecal excretion of 9 9 m T ~ activity is about
`tinely used radiopharrnaceuticals. Detaiied
`50% in 3 days and almost 70% in 8 days.
`pharmacokinetic and metabolic aspects
`of ra-
`Beasley et al. (2) observed that pertechnetate is
`diopharmaceuticals have not been presented, as
`secreted by the salivary glands and gastric
`they are discussed in the following chapters. In
`mucosa and is excreted to a significant degree in
`a few
`instances, scintiphotographs iiluslraling
`normal biodistribution have been included. Fa-
`the feces. The distribution
`of pertechnelate is
`miliarity with the material in this chapter should
`somewhat different from iodide distribution in
`provide better understanding and appreciation
`that iodide is reabsorbed once it passes into the
`of the contents of later chapters.
`1% of the admin-
`small intestine. Also, about
`istered dose of pertechnetate is trapped by the
`thyroid glands.
`
`SODIUM [99mTc]PERTECHNETATE
`99mTc decays with a half-life of
`6 hours and
`emits y-rays of 140 keV with an abundance of
`*Although [99"Tclpertechnetate is preferred by IUPAC,
`90%. This radionuclide is obtained in the chern-
`gQmTc-pertechnetale is standard, and both ax used through-
`ical form of NaTcO, by eluting the 9 9 M ~ - 9 9 m T ~
`out this chapter.
`
`

`

`4
`
`f Essentials of Nuclear Medicine Scieljce
`
`The administered dose varies with the type of
`study: 10-20 mCi for brain imaging, 1-5 mCi
`for thyroid studies, and 20-25 mCi for in vivo
`red blood cell labeling
`for gated blood pool
`sludies. In brain and thyroid studies, imaging is
`performed about 20-30 minutes or longer after
`injection, whereas in gated blood pool studies,
`it is performcd 5-10 minutes after injection.
`Brain imaging with 99mTc0, is governed by
`the blood-brain barrier (BBB) which prevents
`wmTcO, from entering normal brain cells. The
`BBB breaks down, however, in abnormal cells
`such as occur in tumors, infarcts,
`and other
`in le-
`conditions, and thus the tracer localizes
`sions. 99mTcO; localizes in the choroid plexus,
`and thus artifacts are seen in normal brain im-
`ages; this is prevented by oral administration of
`250 mg potassium perchlorate
`to patients
`just
`(3). Potassium
`prior to injection
`of the tracer
`perchlorate saturates the choroid plexus and
`leaves no binding sites for 99mT~O;I
`The normal brain
`scintigraphs do not show
`activity within the cerebrum
`itself due to the
`blood-brain barrier. The periphery of the hemi-
`spheres, however, is outlined by increased ac-
`tivity in the subarachnoid space, calvaria, and
`soft tissues of the scalp. Increased activity is
`also seen in the sagittal and transverse sinuses.
`On h e posterior views, the transverse sinuses
`are generally symmetric. On lateral views, ac-
`tivity is seen in the suprasellar and sylvian
`regions.
`
`Figure 1.1. A normal thyroid scinligraph obtained at
`60 minutes after administration of 5 mCi of
`9 9 m ~ ~ o ~ - .
`
`99mTc07 is trapped in the thyroid but, unlike
`iodide, is not organified. Administration of per-
`chlorate, Lugol's solution, and
`thiocyanate re-
`duces the 9 9 m T ~ uptake by the thyroid glands.
`of 99mTc0, is only
`Normal thyroid uptake
`0.3-3 .O% at 20 minutes after administration. A
`normal scintigraph exhibits a homogeneo