Radiopharmaceuticals in Nuclear Pharmacy & Nuclear Medicine

500 Pages·2004·1.12 MB·English

by  Richard J. Kowalsky

Radiopharmaceuticals
in Nuclear Pharmacy and Nuclear Medicine
Second Edition
•
Radiopharmaceuticals
in Nuclear Pharmacy and Nuclear Medicine
Second Edition
Richard J. Kowalsky, PharmD, BCNP, FAPhA
Associate Professor of Pharmacy
Associate Professor of Radiology
University of North Carolina
Chapel Hill, North Carolina
Steven W. Falen , MD, PhD
Director of Nuclear Medicine and PET Services
Riverside Regional Medical Center
Newport News, Virginia
APhA
•
American Phannacists Association
Washington, D.C.
1 _
•
Editor:NancyTarleton Landis
AcquiringEditor:SandraJ.Cannon
LayoutandGraphics:RoyA.Barnhill
Proofreading:KathleenK.Wolter
Indexing:L.PilarWyman
©2004bytheAmerican Pharmacists Association.
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Library ofCongress Cataloging-in-PublicationData
Kowalsky,RichardJ.
Radiopharmaceuticalsinnuclearpharmacyandnuclearmedicine /
RichardJ.Kowalsky,Steven W.Palen>-2nded.
p.;cm.
Rev.ed. of:Radiopharmaceuticalsinnuclearmedicinepractice.c1987.
Includesbibliographicalreferencesand index.
ISBN1-58212-031-5
1. Radioisotopescanning.2. Radiopharmaceuticals.3. Radioisotopes inpharmacology.
[DNLM:1. Radiopharmaceuticals-diagnostic use.2. Radiopharrnaccllticals--therapeutic use.
3. NuclearMedicine.4. Radiochemistry-methods. WN 440K88r2()().j] I.Palen,StevenW.II.
Kowalsky,RichardJ.Radiopharmaceuticalsin nuclearmedicinepractice.III.TItle.
RC78.7.R4K692()().j
616.07'575--dc22
2004011196
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Acknowledgments
Weowea greatdebtofgratitude toseveral individuals who helped to bring thisbook to
fruition.These peopleincludeJamesF.Cooper,PharmD,for his recommendationsregard
ingbiologiccontrol testing ofradiopharmaceuticals; Marija Ivanovic,PhD,for her recom
mendations on radiation detection, instrumentation, and statistics;Wenbin Lin, PhD, for
his helpful discussions of stereochemistry; Gary Pollack, PhD, for his recommendations
and helpful discussions of pharmacokinetic principles; and Stanley Shaw, PhD, for his
inputon the history of nuclear pharmacy.
Weextend our deep appreciation to the nuclear pharmacystudents at the University
ofNorth Carolina School ofPharmacy who critiqued many of thechaptersand provided
constructive criticism to improve the clarity.These individuals include Miles Bare, Ben
Borders,Song Bui,Thomas Carter,Mark Chen, Radu Ciocan,Chris Cornish,Seboo Dha
khura, Megan Fales, Don Haslam, Sean Hatfield, Hayden Honeycutt, Heather Johnson,
Matt[u, RJKulyk, Angie McKeehan, Cecilia Reyes, Lysa Turner, Matt Wead, and Kevin
Wiltz.
We also are most grateful to our editor, Nancy Landis, for her insights, constructive
suggestions,andattention todetail duringtheeditingofthisbook,andtoJulianGraubart,
Director, Books and Electronic Products Department at APhA, for his guidance and
patience during the writing of this textbook.
Finally,we would like to acknowledgeJ.Randolph Perry, MD,now deceased,theco
authorof the previous edition.His material in thatedition was usefulin the preparation
ofthis one,and several of the images he contributed remain in the current edition.
xi
•
Contents
Preface vii
Acknowledgments xi
Contributors xiii
1 Radiopharmaceuticals, Nuclear Medicine, and NuclearPharmacy:
An Overview 1
2 Radioactive Decay 17
3 Radiation Detection and Measurement 39
4 Radiation Protection and Risk 71
5 Radiation Safety 99
6 Radiation Biology 127
7 Licensing and Regulatory Control 157
NeilA. Petry
8 Radionuclide Production 213
9 Radiopharmaceutical Chemistry 235
10 Radiopharmaceuticals for Positron Emission Tomography 337
StephenM.Moerleill
11 The Nuclear Pharmacy 381
KristinaM. Wittstrom
12 Quality Control in NuclearPharmacy 399
c.
Joseph Hung
13 Brain 451
14 Thyroid 495
15 Hearl 515
16 Lung 561
17 Liver, Spleen, and Gastrointestinal System 589
18 Kidney 633
19 Bone 671
20 Total-Body and Miscellaneous Procedures 695
v
vi
21 Monoclonal Antibodies 733
22 In Vivo Function Studies 753
23 Therapeutic Radiopharmaceuticals 767
Index 789
Preface
Radiopharmaceuticalsin NuctearPharmacy andNuclearMedicine, SecondEdition, follows the
same basic format as its predecessor, Radiophnrmaceuticals ill Nuclear Medicine Practice.
Chapters from that firstedition have been rewritten and updated, and new chapters are
included. The first 12 chapters deal with the physical and chemical properties of radio
pharmaceuticals and theirsafehandlingand control,while the remaining11chaptersdeal
with the biologic properties of radiopharmaceuticals and their clinical application in
nuclearmedicine.
The bookbegins with an overview ofradiopharmaceuticals used in nuclear medicine
and pharmacy, followed by discussions of radioactive decay, radiation detection and
measurement, radiation protection and risk, radiation safety, radiation biology, licensing
and regulatory controls, radionuclide production, radiopharmaceutical chemistry,
positron emission tomography (PET) radiopharmaceuticals, the nuclear pharmacy, and
quality control.Thechapterson radiation biology and PETradiopharmaceuticalsare new
to this edition. Together, these first 12chapters present the essential information needed
for a pharmacist to become an authorized nuclear pharmacist.
Chapter1contains an overview ofthegeneral propertiesofradiopharmaceuticalsand
their distribution patterns after administration and an introduction to the types of proce
dures performed in nuclear medicine.New to thisedition isa historyof the development
ofnuclearpharmacyasaspecialtypractice,coveringkeyevents intheevolutionofnuclear
pharmacy practice, the development of programs for training nuclear pharmacists, and
thecertificationprocessfor recognitionofnuclearpharmacyas the firstpharmacyspecialty
by the Board of PharmaceuticalSpecialties.
The next few chapters expand upon the physical aspects of radiopharmaceuticals,
covered in Chapter 2 in the previous edition. Chapter 2 of this edition reviews atomic
physics, radioactive decay,and radioactivity.Covered in Chapter3are the interactionsof
radiation with matterand instrumentation forradiation detection,plus a new section on
counting statistics.Chapter 4addresses radiation measurement and protection, radiation
dosimetry,and the new topic of radiation riskassessment.
Chapter 5 is a new chapter that expands the topic of radiation safety. It includes a
discussion of radiation protection organizations; radiation safety programs; radiation
safety terms and units; sources of radiation exposure in nuclear pharmacy and nuclear
medicine;personnel and area monitoring; radiation workernotices,reports, and instruc
tions; and the receipt,shipment, and disposalof radioactive material.
Chapter 6is a new chapteron thebiologiceffects of ionizing radiation.Itbegins with
a discussion of the effects of radiation on cellular biologic systems and includes genetic
effects, effects on cell cycles, radiosensitivity, and the effects of dose fractionation. Also
covered are the biologiceffects ofwhole-bodyirradiation,the carcinogenicand hereditary
effects of radiation exposure, radiation effects on the embryo and fetus, and radiation
induced cataractogenesis.
An expanded discussion of licensing and regulatory controlofradioactive material is
presented in Chapter 7, authored by Neil A. Petry, MS, BCNP, of the Duke University
Medical Center in Durham, North Carolina. Itbegins with a review of nuclear pharmacy
practiceguidelines,thendelvesintodrugregulationby theFood and DrugAdministration
and regulation of radioactive material by the Nuclear Regulatory Commission (NRC).
Specific regulations on radiopharmaceuticals, including PET drugs, and investigational
..
new drug (IND), new drug application (NDA), and abbreviated new drug application
(ANDA) processes are described.The chapterconcludes with a comprehensive review of
NRC regulations for the medical use of radiopharmaceuticals, specifically of the newly
revised Part35 regulations in TItle 10of the Code of Federal Regulations.
Chapter8dealswith theproductionof radionuclidesfor medical use. Itcoversnuclear
reactions; radionuc1ides produced in nuclear reactors, cyclotrons, and linearaccelerators;
and generator-produced radionuclides. Generator physics, with emphasis on the 9'ImTc
generator,is also discussed.
Chapter 9isa greatly expanded discussion ofradiopharmaceuticalchemistry,present
ing many recent developments. This chapter includes ideal properties of radiopharma
ceuticals, radiopharmaceutical development and classification, and a basic chemistry
review covering bonding concepts, stereochemistry concepts, and radiometal solution
chemistry. A discussion of technetium chemistry follows, including the development of
first- and second-generation technetium compounds and the preparation and properties
ofspecific technetium radiopharmaceuticals from kits.Adiscussion ofradioiodine radio
pharmaceuticals includes the solutionchemistry ofradioiodine,radioiodination methods,
and the preparation and properties of radiopharmaceuticals labeled with iodine isotopes.
TheremainderofChapter9discusses the chemistryofotherradionuclidesusedin nuclear
medicine (gallium, indium, thallium, xenon, chromium, cobalt, phosphorus, strontium,
yttrium,andsamarium)and thepreparationandpropertiesof theirradiopharmaceuticals.
Chapter 10 is a new chapter on PET radiopharmaceuticals, authored by Stephen M.
Moerlein, PhD, BCNP, of the Mallinckrodt Institute of Radiology in SI. Louis, Missouri.
It covers the basic concepts of PET, including scanner design and data acquisition,
PET/computed tomography (CT) scanners, and imaging applications including blood
flow, metabolism, and neuroreceptor studies.Reimbursable PETprocedures for oncology,
neurology, and cardiology are discussed,as are production of PET nuclides from genera
torsandcyclotrons.AthoroughdiscussionofPETradiopharmaceuticalchemistry includes
thepreparation and properties of radiolabelingprecursors, !'ETradiopharmaceuticalsyn
thesis, and systems for preparing !'ETdrugs forclinicaluse.Also included in the chapter
areadiscussionofreformulationproceduresused in PETradiopharmaceuticalpreparation
and a brief discussion of quality assurance and regulatory issues related to PET radio
pharmaceuticals.
Chapter 11, on the nuclear pharmacy, was authored by Kristina M. Wittstrom, BS,
BCN!', of the University of New Mexico in Albuquerque and begins with a brief history
ofthe developmentofnuclearpharmacy.Itthencovers facilitiesand equipmentnecessary
to operate a nuclearpharmacy, radiation detection instrumentation, ancillary equipment
and supplies, and personnel. Nuclear pharmacist responsibilities are discussed; these
include radiopharmaceutical procurement,compounding, quality assurance, dispensing,
distribution, health and safety issues in practice, professional consultation, and the mon
itoring of patient outcomes. The chapter concludes with a discussion of record-keeping
issues.
Chapter 12is an in-depth discussion of radiopharmaceutical quality control,authored
c.
by Joseph Hung, MS, PhD, BCNI~ of the Mayo Clinic in Rochester, Minnesota. An
overview of quality control is followed by discussion of specific areas, including radio
nuclide,radiochemical,pharmaceutical,andbiologicconsiderations. The chaptercompre
hensively covers the instrumentation and methods used to assess radiopharmaceutical
identity, quantity, and purity. A discussion of instrumentation quality control includes
dose calibrators and survey instruments. The chapter ends with a discussion of quality
control issues specific to PET drug products.
The remaining 11chapters cover the diagnostic and therapeutic use of radiopharma
ceuticals. Chaptersonspecificbodysystems(brain; thyroid; heart; lung; liver,spleen, and
ix
gastrointestinal tract; kidney; and bone) are followed by a chapter on total body proce
dures.Two new chapters covermonoclonalantibodies and therapeutic radiopharmaceu
ticals.Thiseditionretains thechapteron invivofunctionstudiesfrom theprevious edition,
butthe chapter on in vitro studies has been removed because these studies are no longer
a significant partof nuclearmedicine practice.
Chapters 13 through 20, on the major organ systems, follow the same format. Each
discusses physiologic processes important to the localization of imaging agents and
describes the development of radiopharmaceuticals used to study the particular organ
system. The focus is on current agents of choice, their biologic properties, and their
mechanisms oflocalization.The chapters conclude witha discussion ofnuclear medicine
procedures, including the rationale,pharmaceuticalchoices, and interpretation ofresults.
Images are included to illustrate normal and abnormalstudies.
Chapter 21,on monoclonalantibodies for diagnostic use, begins with a review of the
immune system and proceeds with a discussion of antibody structure, classification,
development, modification, antibody-antigen interactions, and nomenclature. General
antibody labeling methods are discussed, as are specific diagnostic antibodies and their
preparation, properties, and use.
Chapter 22 covers in vivo function studies. These nonimaging studies include blood
volume measurement and tests for vitamin B" deficiency. The underlying principles
involved in each study and the radiopharmaceuticals used are discussed.
Chapter 23 is a new chapter on therapeutic radiopharmaccuticals, including mono
clonal antibodies. It begins with a discussion of radioimmunotherapy principles and
radionuclide and antibody requirements for treating tumors.Thisisfollowedby adiscus
sion of methodsused in radioimmunotherapyand a description ofthepreparation, prop
erties, and use of therapeutic monoclonal antibodies. The chapter concludes with a dis
cussionofnon-antibodytherapeuticradiopharmaceuticals:radiotherapyofbonepainand
"Ptherapyforpolycythemia,effusions,andradiationsynovectomy.Thechapterconcludes
with a brief discussion of brachytherapy for brain tumors using the 1251product lotrex.
Some 150 tables and 440 figures are included to enrich and illustrate the text. Each
chapter is referenced to the primary literature so that readers can find more detailed
information on a topic.The comprehensive nature of this book makes it suitable for use
as a reference by nuclear pharmacy practitioners, nuclear medicine technologists, and
nuclear medicine physicians. The book should also be useful in programs for educating
these practitioners.
Although the title of this edition emphasizes nuclear pharmacy, emphasis on radio
pharmaceuticaluse innuclearmedicine hasnot decreased;thebookhas expandedinboth
areas. The work of four co-authors who are both practitioners and educators not only
helped us complete thebook butenriched itscontent. Weare gratefulfortheir willingness
to add this work to their busy professional lives.
Richard J.Kowalsky
Steven W. Falen
2004