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Practical Nuclear Medicinei

Peter F. Sharp, Howard G. Gemmelland Alison D. Murray (Eds)Practical NuclearMedicineThird EditionWith 222 Figures including 17 Color Platesiii

Peter F. Sharp, PhD, FInstP, FIPEM, FRSEDepartment of Biomedical Physics and BioengineeringAberdeen University and NHS Grampian, UKHoward G. Gemmell, PhD, FIPEMDepartment of Nuclear MedicineAberdeen Royal InfirmaryNHS Grampian, UKAlison D. Murray, FRCP, FRCRDepartment of RadiologyUniversity of Aberdeen, UKThe authors wish to acknowledge their gratitude to OUP for the use of the following figures from thesecond edition of this book:1.6, 1.7, 2.1, 2.3, 2.4, 2.5, 2.7, 3.1, 3.3, 3.5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 5.10, 5.11, 5.12, 6.1,6.2, 7.1, 7.4, 7.5, 7.6, 7.7, 10.1, 10.2, 10.3, 10.4, 10.8, 13.1, 13.10, 13.14, 13.15, 13.16, 14.1, 14.2, 14.3,14.4, 14.5, 14.9, 14.10, 14.11, 14.12, 14.13, 14.14, 15.1, 15.4British Library Cataloguing in Publication DataA catalogue record for this book is available from the British LibraryLibrary of Congress Cataloguing-in-Publication DataSharp, Peter F.Practical nuclear medicine/Peter F. Sharp, Howard G. Gemmell, Alison D. Murray.–3rd ed.p. cm.Includes bibliographical references and index.ISBN 1-85233-875-X (alk. paper)1. Nuclear medicine. I. Gemmell, H. G. II. Murray, Alison D. III. Title.R895.S45 20052004061448616.07 575–dc22Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under theCopyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form orby any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordancewith the terms of licences issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those termsshould be sent to the publishers.ISBN-10: 1-85233-875-X3rd editionISBN-13: 978-1-85233-875-6Printed on acid-free paperFirst published in 1996 by Oxford University Press; ISBN 0199630321Second edition published in 1998 Oxford University Press; ISBN 0192628429Third edition 2005 C Springer–Verlag London Limited 2005The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, thatsuch names are exempt from the relevant laws and regulations and therefore free for general use.Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained inthis book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature.Printed in Singapore9 8 7 6 5 4 3 2 1(TB/KYO)SPIN 10931226Springer Science Business Mediaspringeronline.comiv

ForewordThere have been several significant advances in nuclear medicine since the publication of thesecond edition of Practical Nuclear Medicine. The last seven years have seen great strides ininstrumentation, including new coincidence detectors, the development of a wider varietyof crystals, and the advent of combined anatomical/functional imaging devices, includingPET/CT and SPECT/CT. PET imaging with 18 F-FDG has become a mainstay of manyclinical settings, and other radiotracers are finding their way into the rapidly expanding fieldof oncologic PET. However, radiopharmaceutical breakthroughs during this period havenot been confined to one single imaging modality. Refinements in diagnostic applicationsof monoclonal antibodies, radiolabeled peptides, neuroreceptors, and a whole spectrumof new molecular targeting agents are steadily strengthening the clinical nuclear medicinearmamentarium.Such a daunting array of changes can present quite a challenge to even the most experienced nuclear medicine practitioner. Consider then the magnitude of complexitiesthat physicians, physicists, and technologists who are just beginning their training in ourfield are expected to assimilate! That is precisely why this book offers an easily accessibleapproach to both the basic science groundwork and the clinical applications of nuclearmedicine. The third edition presents its material in a very pragmatic manner by disseminating the various contributors’ practical experience via detailed instructions. The breadthof this hands-on knowledge and advice will likely benefit readers at all levels of expertise.The book’s concentration on the actual practice of nuclear medicine is particularly discernible in the first few chapters, which address scientific foundations of SPECT, PET, radiopharmaceuticals, etc. Such topics as instrumentation, data processing, and non-imagingradionuclide tests are covered in a way that accentuates specific human interaction; thus,quality assurance is an oft-recurring theme. To reflect the growing importance of PET inthe clinical arena, the introductory chapter on this subject has been expanded and a newchapter on current PET radiopharmaceuticals and PET imaging in oncology, neurology,and cardiology has been added. In addition, new contributors have prepared the chapterson the skeletal system, the cardiovascular system, and the urinary tract.This third edition of Practical Nuclear Medicine continues the text’s tradition of guidingreaders through not only the most commonly performed clinical nuclear medicine testsbut the scientific bases on which they were built. In addition, the editors of this version haveskillfully weeded out certain procedures and de-accentuated others whose use has lessenedin the clinical setting over the last few years. These efforts have produced a clinical manualthat clearly addresses many of the diagnostic dilemmas that currently appear in nuclearmedicine, which is constantly expanding the limits of its instrumentation, radiopharmaceuticals, and diagnostic capabilities. In the future, many aspects of current molecularimaging research (such as targeting of tumor antigens, receptors, and metabolism; imaging of hypoxia and apoptosis; and antisense targeting for both diagnosis and therapy)will find their way into the clinical setting. Therefore, it is of paramount importance thatindividuals working in nuclear medicine update their skills today in preparation for thev

viFOREWORDnext wave of advanced knowledge and clinical techniques. Fortunately, the third edition ofPractical Nuclear Medicine will assist members of our community in accomplishing thattask, and the editors and contributors are to be commended for making this possible.Martin P. Sandler, MDCarol D. and Henry P. Professor and ChairmanDepartment of Radiology and Radiological SciencesVanderbilt University School of MedicineNashville, Tennessee, USA

ContentsForeword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Martin P. Sandler . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .vix1. Nuclear Medicine ImagingPeter F. Sharp and Keith A. Goatman . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12. Single Photon Emission Computed Tomography (SPECT)Howard G. Gemmell and Roger T. Staff . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .213. Positron Emission TomographyPeter F. Sharp and Andy Welch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .354. Non-Imaging Radionuclide InvestigationsAlex T. Elliott and Thomas E. Hilditch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .495. Quality AssuranceAlex T. Elliott . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .656. Radiation ProtectionPhilip P. Dendy, Karen E. Goldstone, Adrian Parkin,and Robert W. Barber . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .917. The RadiopharmacyJames Doherty and David Graham . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1138. The Skeletal SystemMargaret E. Brooks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1439. The Cardiovascular SystemMalcolm J. Metcalfe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16310. The LungHenry W. Gray . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179vii

viiiCONTENTS11. The Urinary TractPhilip S. Cosgriff . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20512. The Brain, Salivary and Lacrimal GlandsAlison D. Murray . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23113. Thyroid, Parathyroid, and Adrenal Gland ImagingWilliam H. Martin, Martin P. Sandler, and Milton D. Gross . . . . . . . . . . . . . . 24714. Gastrointestinal Tract and LiverLeslie K. Harding and Alp Notghi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27315. Infection and InflammationA. Michael Peters and Heok K. Cheow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30516. Tumor ImagingAlan C. Perkins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33317. Clinical PET ImagingGary J. R. Cook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365

ContributorsRobert W. Barber, MSc, BScDepartment of Medical Physics, Addenbrooke’sHospital, Cambridge, UKKaren E. Goldstone, BSc, MScDepartment of Medical Physics, Addenbrooke’sHospital, Cambridge, UKMargaret E. Brooks, MB ChB, FRCP, DMRD,FRCRDepartment of Nuclear Medicine, AberdeenRoyal Infirmary, Aberdeen, UKDavid Graham, MSc, BSc, MRPharmSPharmacy Department, Aberdeen RoyalInfirmary, Aberdeen, UKHeok K. Cheow, MB ChB, MRCP, FRCRDepartment of Nuclear Medicine,Addenbrooke’s Hospital, Cambridge, UKGary J. R. Cook, MB BS, MDDepartment of Nuclear Medicine and PET,Royal Marsden Hospital, Sutton, UKPhilip S. Cosgriff, BSc, MScMedical Physics Department, Pilgrim Hospital,Boston, UKPhilip P. Dendy, PhDDepartment of Medical Physics, Addenbrooke’sHospital, Cambridge, UKJames Doherty, BSc, MRPharmSPharmacy Department, Aberdeen RoyalInfirmary, Aberdeen, UKAlex T. Elliott, BA, PhD DSc, CPhys, FInstP,FIPEM, ARCPDepartment of Clinical Physics andBioengineering, Western Infirmary, Glasgow,UKHoward G. Gemmell, BSc, MSc, PhD, FIPEMDepartment of Nuclear Medicine, AberdeenRoyal Infirmary, NHS Grampian, Aberdeen,UKKeith A. Goatman, BEng, MSc, PhDDepartment of Bio-Medical Physics andBio-Engineering, University of Aberdeen, UKHenry W. Gray MD, FRCP, FRCRDepartment of Nuclear Medicine,Royal Infirmary, Glasgow, UKMilton D. Gross, MDDepartments of Radiology and InternalMedicine, University of Michigan MedicalSchool, Nuclear Medicine Service,Department of Veterans Affairs Health System,Ann Arbor, MI, USALeslie K. Harding, MB ChB, BSc, FRCP, FRCRDepartment of Physics and Nuclear Medicine,City Hospital NHS Trust, Birmingham, UKThomas E. Hilditch, BSc, PhD, FInstPDepartment of Clinical Physics andBioengineering, Western Infirmary,Glasgow, UKMalcohm J. Metcalfe, MD, FRCPDepartment of Cardiology, Aberdeen RoyalInfirmary, Aberdeen, UKWilliam H. Martin, MDDepartment of Radiology and RadiologicalSciences, Vanderbilt University Medical Center,Nashville, TN, USAAlison D. Murray, MB ChB, FRCP, FRCRDepartment of Radiology, College of LifeSciences and Medicine, University of Aberdeen,UKix

xCONTRIBUTORSAlp Notghi, MD, MSc, FRCPDepartment of Physics and Nuclear Medicine,City Hospital NHS Trust, Birmingham,UKMartin P. Sandler, MDDepartment of Radiology and RadiologicalSciences, Vanderbilt University Medical Center,Nashville, TN, USAAdrian Parkin, DPhilDepartment of Medical Physics, Addenbrooke’sHospital, Cambridge, UKPeter F. Sharp, BSc, PhD, CPhys, FInstP, ARCP,FIPEM, FRSEDepartment of Bio-Medical Physics andBio-Engineering, University of Aberdeen andNHS Grampian, UKAlan C. Perkins, BSc, MSc, Ph.D, FIPEM, ARCPDepartment of Medical Physics, MedicalSchool, Queen’s Medical Centre, Nottingham,UKA. Michael Peters, MA, MD, MSc, FRCPath,FRCP, FRCR, FMedSciDepartment of Applied Physiology, BrightonSussex Medical School, University of Sussex,Brighton, UKRoger T. Staff, PhDDepartment of Bio-Medical Physics andBio-Engineering, University of Aberdeen andNHS Grampain, UKAndy Welch, BSc, PhDBiomedical Physics and Bioengineering, BSc,PhD, University of Aberdeen, UK

1Nuclear Medicine ImagingPeter F. Sharp and Keith A. Goatman1.1 IntroductionIn nuclear medicine clinical information is derived from observing the distribution of a pharmaceutical administered to the patient. By incorporating a radionuclide into the pharmaceutical,measurements can be made of the distribution ofthis radiopharmaceutical by noting the amount ofradioactivity present. These measurements maybe carried out either in vivo or in vitro. In vivoimaging is the most common type of procedurein nuclear medicine, nearly all imaging being carried out with a gamma camera (see Section 1.3).Nuclear medicine is intrinsically an imaging technique showing the body’s biochemistry, the particular aspect depending upon the choice of theradiopharmaceutical. This is in contrast to othercommonly used imaging procedures whose mainstrengths are showing anatomy.Where a knowledge of the precise amountof activity present in an organ is required thenpositron emission tomography can provide this(see Chapter 3), although while its usage is increasing it still remains a specialized technique.If an image of the distribution is not essential,collimated scintillation probe detectors alignedwith the organ of interest may be used [1]. Ifthe amount of radioactivity present is very lowthen high-sensitivity whole body counters, consisting of heavily shielded probe detectors, arenecessary [2].In vitro measurements are made on samples ofmaterial taken from the patient, such as breath,blood, urine, and feces, to determine the amountof radiopharmaceutical present. Such measurements are made using the gamma- or beta-samplecounting techniques discussed in Chapter 4.The diagnostic information is provided by theaction of the pharmaceutical; the role of the radioactivity is purely a passive one, enabling theradiopharmaceutical to be localized. For this reason it is possible to use low levels of radioactivityand so the potential hazard to the patient can bekept small (see Chapter 6).1.2 The IdealRadiopharmaceuticalThe specific features looked for in the ideal radiopharmaceutical are summarized in Table 1.1.It must be emphasized, however, that no singleradiopharmaceutical actually has all these properties. As the radionuclide label and the pharmaceutical perform different functions, the particularfeatures regarded as desirable for them can largelybe considered separately.1.2.1 RadionuclidesHalf-lifeThe half-life of the radionuclide determines howquickly the radioactivity will decay. Obviously, ifthe half-life is very short then the activity will havedecayed to a very low level before imaging hasstarted. On the other hand, if it is too long then1

2PRACTICAL NUCLEAR MEDICINETable 1.1. Ideal characteristics of a radiopharmaceuticalHalf-life should be similar to the length of the testThe radionuclide should emit gamma rays and there shouldbe no charged particle emissionsThe energy of the gamma rays should be between 50 and300 keVThe radionuclide should be chemically suitable for biologicalbehaviorThe radionuclide should be readily available at the heareaofinterestThe pharmaceutical should be eliminated from the body witha half-life similar to the duration of the examinationThe radiopharmaceutical should be simple to preparethe patient will remain radioactive for a considerable time and in order to reduce the possibilityof radiation damage the amount of activity administered will have to be kept low. Roughly, thehalf-life should be of a similar length to that of theexamination, usually a few hours.Type and Energy of EmissionFor imaging it is first necessary that the radiationgiven off should be sufficiently penetrating to allow it to be detected externally even though it mayneed to pass through several centimeters of tissue.This limits the choice to gamma rays or X-rays.The energy of the radiation will also affect its ability to penetrate tissue: the higher the energy thebetter it will be. However, the higher the energythe more difficult it will be to stop the gamma rayin the detector of the imaging device. In practicegamma rays with energies between 50 keV and 300keV are preferred, about 150 keV being ideal.The radiation dose received by the patient mustalso be considered. It is necessary to avoid thoseradionuclides that have significant particulate (i.e.alpha and beta) emissions which, owing to theirshort range, will simply increase radiation dosewithout contributing to the image. As the purposeof radioactive decay is to redress an imbalance inthe ratio of protons to neutrons in the nucleus, itis clear that simple gamma decay will be accompanied by the emission of a charged particle, usuallya beta particle. There are, however, two decay processes that avoid this problem: isomeric transitionand electron capture. Particles will still be emitted,namely Auger and conversion electrons, but at aconsiderably lower rate than the one per gammaexperienced with other modes of decay.Pharmaceutical LabelingWhile the prime consideration in choosing a radionuclide is that its manner of decay should besuitable for in vivo imaging, it must not be forgotten that this material must be incorporatedinto a pharmaceutical. Unfortunately all the elements of biological interest, such as carbon, nitrogen, and oxygen, do not have radioisotopesmeeting the criteria of Table 1.1. These particular elements do, however, have radioisotopes thatemit positrons. These positively charged electronsannihilate with an electron to produce a pair of511 keV gamma rays. While the energy of thesegamma rays is such that the sensitivity of detection in the crystal of a standard gamma camerawill be low, nevertheless cameras are available thatwill do both single photon and positron imaging, either by employing a high-energy collimator or, more commonly, by using coincidenceelectronics. The most effective way of imagingpositron emitting radiopharmaceuticals is, however, with specialized equipment, described inChapter 3.Despite the potential problems, pharmacistsand radiochemists have been very successful inincorporating some of the most unlikely material, such as the widely used radioisotope of technetium, into a large range of pharmaceuticals. Thisproblem will be considered in Chapter 7.Production of RadionuclidesRadionuclides can be produced from threesources: the nuclear reactor, the cyclotron, or agenerator. It is not intended to go into detail aboutthe process of production of radioactive materialand the interested reader is recommended to readOtt et al [3].The reactor radionuclides are produced eitherby introducing a target of stable material into theneutron flux found inside the reactor, or by separating out fission products from the fuel rodsor a uranium target. As neutron irradiation increases the number of neutrons relative to thenumber of protons in the nucleus, it will produceradionuclides that decay predominantly by betadecay.The cyclotron produces a beam of charged particles, such as alpha particles or deuterons, whichis used to bombard a target material. The re

Practical nuclear medicine/Peter F. Sharp, Howard G. Gemmell, Alison D. Murray.–3rd ed. p. cm. Includes bibliographical references and index. ISBN 1-85233-875-X (alk. paper) 1. Nuclear medicine. I. Gemmell, H. G. II. Murray, Alison D. III. Title. R895.S45 2005 616.07 575–dc22 2004061448 Apart from any fair dealing for the purposes of research or private study, or criticism or review, as .

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