Table Of ContentH.-J.Biersack·L.M.Freeman(Eds.)ClinicalNuclearMedicine
Hans-Jürgen Biersack · Leonard M. Freeman (Eds.)
Lionel S. Zuckier · Frank Grünwald (Associate Eds.)
Clinical Nuclear Medicine
With310Figuresin1,232Partsand91Tables
Hans-JürgenBiersack,M.D.
ProfessorandChairman
DepartmentofNuclearMedicine
UniversityHospitalBonn
Sigmund-Freud-Straße15
D-53127Bonn
Germany
LeonardM.Freeman,M.D.
ProfessorofNuclearMedicineandRadiology
AlbertEinsteinCollegeofMedicine
Director,Dept.ofNuclearMedicine
MontefioreMedicalCentre/MosesDivision
111East210thStreet
Bronx,NY10467
USA
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Preface
Themoderneraofradionuclideimagingandtherapyiswellintoitsseventhdecade.
Duringthisera,manynationalandinternationaltextbookshavebeenpublishedin
anattempttoeducatenotonlythepractitionersofourmedicaldiscipline,butalso
referringphysiciansandmedicalstudents.Someofthemorerecentlargemulticul-
turaltexts,suchasthosebyEllandGhambir,Sandleretal.andHenkinetal.,provide
uswithverycomprehensivereferencesourceswhilesomeofthesmallertextstotally
writtenbytwoorthreeindividuals,e.g.Mettler&GuiberteauandZiessman,O’Mal-
ley&Thrall,haveachievedpopularitywithradiologyresidentsandotherphysicians
intraining.
TheconceptofClinicalNuclearMedicinearose3yearsagofromaconversation
betweentheeditors,whohavebeenclosefriendsformanyyears.Wehavealwaysfelt
that our relationship epitomizes one of the major strengths of nuclear medicine,
whichistheveryclosetiesandspiritofeducationalcooperationthatexistbetween
internationalcolleagues.Weallsharethesameaimofdoingwhateverwecantoopti-
mize patient care whether it be by introducing new pharmaceuticals and instru-
ments or by developing new techniques or approaches to performing our broad
spectrumofclinicalprocedures.Nuclearmedicinephysicianshavealmostuniformly
beenwillingtosharetheirexpertiseatnationalandinternationalmeetings.Thein-
ternationalnuclearmedicinecommunity,unlikemanyotherlargerspecialtyareas,
hasremainedrelativelysmall.
ItwaswithinthisspiritthatClinicalNuclearMedicinewasborn.Aswillbecome
immediatelyevident,thechaptersarealmostequallysplitbetweenAmericanand
Europeanauthors.Additionally,oneofthechapterswascontributedbyoneofour
colleaguesfromTaiwan.AuniquefeatureofthistextistheincorporationofPETinto
eachorgansystemordiseasespecificchapterratherthanpresentingitasaseparate
chapter.Aconsiderableamountoftimewasspentselectingandassemblingthestel-
larcastofauthors,whohavegraciouslycontributedtheirtime,effortand,indeed,
greattalenttomakethistextthereadable,concisetextthatwebelieveitrepresents.
Wehopethatyou,ourreaders,agree.Wearemostgratefultoourmanycolleagues
andfriendswhoshareourvision.
Hans-JürgenBiersack,MD
LeonardM.Freeman,MD
Contents
1 Physics,Instrumentation,andRadiationProtection
P.Zanzonico,S.Heller ....................................... 1
1.1 Introduction .................................................. 1
1.2 BasicPhysics .................................................. 1
1.2.1 AtomicandNuclearStructure ................................... 1
1.2.2 Radioactivity.................................................. 4
1.2.2.1 NuclearInstability ............................................. 4
1.2.2.2 ModesofRadioactiveDecay ..................................... 4
1.2.2.3 MathematicsofRadioactiveDecay................................ 4
1.2.3 InteractionsofRadiationwithMatter ............................. 6
1.2.3.1 ElasticandInelasticInteractions ................................. 6
1.2.3.2 Photon(X-and *-ray)Interactions ............................... 6
1.2.3.3 Particulate-RadiationInteractions ................................ 7
1.3 RadiationDetectionandMeasurement ............................ 7
1.3.1 StatisticalConsiderations ....................................... 7
1.3.2 RadiationDetectorPerformance ................................. 8
1.3.3 BasicDesignandOperatingPrinciplesofRadiationDetectors ........ 9
1.3.4 IonizationDetectors............................................ 9
1.3.5 ScintillationDetectors .......................................... 10
1.4 NuclearMedicineInstrumentation ............................... 11
1.4.1 IntraoperativeProbes........................................... 11
1.4.2 OrganUptakeProbes ........................................... 12
1.4.3 GammaCameras .............................................. 13
1.4.4 TomographicScanners.......................................... 14
1.4.4.1 Introduction .................................................. 14
1.4.4.2 SPECTDataAcquisition ........................................ 15
1.4.4.3 PETDataAcquisition........................................... 15
1.4.4.4 DataProcessingandTomographicImageReconstruction ............ 19
1.4.5 GammaCameraPerformanceandQualityControl .................. 23
1.4.6 Multi-modalityDevicesandOtherDevelopments ................... 26
1.5 RadiationSafety ............................................... 27
1.5.1 RegulatoryJurisdictionandLicensure............................. 27
1.5.2 QuantitiesandUnits ........................................... 27
1.5.3 SourcesofRadiationExposureandDoseLimits .................... 28
1.5.4 PersonnelDosimetry ........................................... 29
1.5.5 Receipt,Transport,Storage,andInventoryofRadioactiveMaterials.....30
1.5.6 RadiationSurveys.............................................. 30
1.5.7 WasteDisposal ................................................ 31
1.5.8 RadionuclideTherapyandthe„New“ReleaseCriteria ............... 31
1.5.9 Record-Keeping ............................................... 32
1.5.10 “Sensitive“PatientPopulations................................... 32
1.5.11 ConcludingRemarks ........................................... 33
References ........................................................... 33
VIII Contents
2 RadiochemistryandRadiopharmacy
S.Guhlke,A.M.Verbruggen,S.Vallabhajosula ................ 34
2.1 RadiochemistryandRadiopharmacyofSPECTTracersandforInternal
Radiotherapy
S.Guhlke,A.M.Verbruggen................................... 34
2.1.1 ProductionofRadionuclidesforSPECTandRadiotherapy ........... 34
2.1.1.1 Introduction .................................................. 34
2.1.1.2 ProductionModes ............................................. 34
2.1.1.3 “Diagnostic“RadionuclidesforSPECTApplications................. 36
2.1.1.4 TherapyNuclides .............................................. 38
2.1.2 RadiopharmaceuticalChemistryofSPECTTracers .................. 39
2.1.2.1 Technetium-99m............................................... 39
2.1.2.2 Iodine-123 .................................................... 44
2.1.2.3 Indium-111 ................................................... 46
2.1.3 RadiopharmaceuticalsforInternalRadiotherapy ................... 46
2.1.3.1 Introduction .................................................. 46
2.1.3.2 RadiochemistryUsingTherapyNuclides .......................... 47
2.1.3.3 Yttrium-90,Bismuth-212/213andLanthanides(e.g.,Samarium-153,
Lutetium-177) ................................................. 48
2.1.3.4 Rhenium-186/188 .............................................. 48
2.1.3.5 Iodine-131andAstatine-211 ..................................... 48
2.1.3.6 DirectElectrophilicSubstitution ................................. 49
2.1.3.7 Iododemetallation ............................................. 49
2.1.3.8 DirectNucleophilicSubstitution ................................. 50
2.1.3.9 ProstheticGroups.............................................. 50
2.2 RadiopharmaceuticalsforPET
S.Vallabhajosula............................................ 50
2.2.1 Introduction .................................................. 50
2.2.1.1 RadionuclidesforPET .......................................... 51
2.2.2 PETRadiopharmaceuticals:MechanismsofCellularUptake
andLocalization ............................................... 52
2.2.2.1 Tissue/OrganPerfusion ......................................... 53
2.2.2.2 Metabolism ................................................... 53
2.2.2.3 DNASynthesis ................................................ 54
2.2.2.4 AminoAcidTransportandProteinSynthesis....................... 54
2.2.2.5 ReceptorBinding .............................................. 55
2.2.2.6 NeurotransmitterSystems ...................................... 55
2.2.2.7 q-AmyloidPlaques ............................................. 57
2.2.2.8 Hypoxia ...................................................... 57
2.2.2.9 GeneExpression ............................................... 58
2.2.3 ProductionofPositronEmittingRadionuclides..................... 58
2.2.3.1 Cyclotrons .................................................... 59
2.2.3.2 NuclearReactions.............................................. 60
2.2.3.3 NuclearReactionsfortheProductionofPositronEmitters ........... 61
2.2.3.4 GeneratorProducedPositronEmitters ............................ 63
2.2.4 RadiochemistryofPETRadiopharmaceuticals ..................... 64
2.2.4.1 OrganicPrecursorsforPET...................................... 64
2.2.4.2 Fluorine-18Radiochemistry ..................................... 65
2.2.4.3 Carbon-11Radiochemistry ...................................... 68
2.2.4.4 RadiochemistryofMetallicRadionuclides ........................ 69
2.2.4.5 AutomatedSynthesisModules .................................. 72
References .......................................................... 72
Contents IX
NuclearMedicineDiagnosis
3 Brain
R.L.VanHeertum,M.Ichise ................................. 77
3.1 SPECTandPETBrainImagingintheEvaluationofCerebro-
vascularDisease ............................................. 77
3.2 SPECTandPETBrainImagingintheEvaluationofDementia ...... 77
3.3 SPECTandPETBrainImagingintheEvaluationofBrainTumors ... 78
3.3.1 Neuroimaging ............................................... 78
3.3.2 BrainSPECTImaging......................................... 79
3.3.3 PETBrainImaging ........................................... 79
3.3.4 Strengths ................................................... 79
3.3.5 Weaknesses ................................................. 80
3.4 SPECTandPETBrainImagingintheEvaluationofSeizureDisorders 80
3.4.1 IncidenceandPrevalence–SeizureDisorders .................... 80
3.4.2 IncidenceandPrevalence–Epilepsy ............................ 80
3.4.3 ClinicalDiagnosis............................................ 80
3.4.4 SPECTBrainImaging......................................... 81
3.4.5 PETBrainImaging ........................................... 81
3.4.6 SPECTandPETImagingoftheDopamineSysteminMovement
Disorders ................................................... 82
3.4.7 DiagnosticUtilityofDopaminePETandSPECT .................. 83
3.4.8 PETandSPECTasaBiomarkerofDiseaseProgression ............ 85
3.5 SPECTandPETImagingoftheDopamineSysteminPsychiatric
Disorders ................................................... 86
3.5.1 PETandSPECTasaTooltoUnderstandPathophysiology .......... 87
3.5.2 PETandSPECTinDrugActionandDevelopmentofNewDrugs .... 88
3.6 BrainDeathScintigraphy...................................... 88
3.7 RadionuclideCerebrospinalFluidFlowStudies ................... 89
References .......................................................... 91
4 Heart
M.D.Cerqueira,M.J.VidigalFerreira ....................... 95
4.1 MyocardialPerfusionImaging ................................. 95
4.1.1 HistoricalPerspective......................................... 95
4.1.2 BasisofMyocardialPerfusionImaging .......................... 95
4.1.3 RadiopharmaceuticalsandImagingProtocols .................... 96
4.1.3.1 Thallium-201................................................ 96
4.1.3.2 Technetium-99mRadiotracers ................................. 97
4.1.3.3 PharmacologicStressAgentsandProtocols ...................... 99
4.1.4 SPECTImageAcquisition ..................................... 102
4.1.5 ProcessingProtocols.......................................... 102
4.1.6 QuantitativeAnalysisofPerfusion .............................. 102
4.1.7 ECGGating ................................................. 103
4.1.8 AcquisitionOptions .......................................... 103
4.1.9 ImageInterpretationandReporting ............................ 103
4.1.10 GeneratingaReport .......................................... 105
4.1.11 ClinicalIndications........................................... 105
4.1.11.1 DiagnosisofCAD ............................................ 105
4.1.11.2 ChestPainintheEmergencyDepartment........................ 109
4.1.11.3 MyocardialPerfusionImagingBeforeandAfterRevascularization... 109
4.1.11.4 RadionuclideImagingBeforeNoncardiacSurgery................. 109
4.2 AssessmentofVentricularFunction............................. 110
4.2.1 HistoricalPerspective......................................... 110
4.2.2 EquilibriumRadionuclideAngiocardiography.................... 110
4.2.2.1 Technique................................................... 110
4.2.2.2 ClinicalIndications........................................... 113
X Contents
4.2.3 FirstPassRadionuclideAngiography............................. 113
4.2.3.1 InstrumentationandProcedure ................................. 113
4.3 HeartFailureandAssessmentofViability......................... 114
4.3.1 Introduction ................................................. 114
4.3.2 SPECTMethods............................................... 114
4.3.3 PETMethods ................................................. 114
4.3.4 NeurocardiacImaging ......................................... 114
References .......................................................... 114
5 Lung
M.Bajc,B.Jonson,H.C.Steinert .............................. 118
5.1 ConventionalandSPECTLungImaging
M.Bajc,B.Jonson............................................ 118
5.1.1 IntroductionandHistoricalPerspective .......................... 118
5.1.2 Radiopharmaceuticals ......................................... 118
5.1.2.1 VentilationScintigraphy........................................ 118
5.1.2.2 PerfusionScintigraphy......................................... 119
5.1.3 V/P Method .............................................. 119
SPECT
5.1.3.1 Acquisition................................................... 119
5.1.4 ClinicalApplication ........................................... 120
5.1.4.1 PulmonaryEmbolism.......................................... 120
5.1.4.2 Interpretation:ProbabilisticVersusHolistic ....................... 121
5.1.4.3 Pitfalls ...................................................... 124
5.1.4.4 SelectionofTherapeuticStrategy ................................ 125
5.1.4.5 Follow-up.................................................... 125
5.1.5 ComputedTomographicAngiographyinDiagnosisofPulmonary
Embolism.................................................... 125
5.1.5.1 Interpretation ................................................ 125
5.1.5.2 Pitfalls ...................................................... 126
5.1.5.3 SensitivityandSpecificityofV/P andCTinDiagnosisofPE ..... 126
SPECT
5.1.5.4 AlternativeDiagnosis .......................................... 127
5.1.6 AncillaryFindingswithV/P ................................ 127
SPECT
5.1.6.1 ReverseMismatchDefects ...................................... 127
5.1.6.2 ChronicObstructivePulmonaryDisease.......................... 127
5.1.6.3 HeartFailure ................................................. 127
5.1.6.4 Pneumonia................................................... 128
5.1.7 PositronEmissionTomography ................................. 133
5.1.7.1 VentilationandPerfusion ...................................... 133
5.1.7.2 RadiationExposure ........................................... 134
5.1.7.3 AlgorithmforEvaluationofPatientsSuspectedofHavingPE ........ 134
5.1.8 ConcludingRemarks .......................................... 134
References .......................................................... 135
5.2 PETandPET/CTinLungCancer
H.C.Steinert................................................ 137
5.2.1 Introduction ................................................. 137
5.2.2 Radiopharmaceuticals ......................................... 137
5.2.3 PETImaging ................................................. 137
5.2.4 IntegratedPET/CTImaging..................................... 138
5.2.5 Non-SmallCellLungCancer .................................... 139
5.2.5.1 SolitaryPulmonaryNodule ..................................... 140
5.2.5.2 StagingofthePrimaryTumor................................... 141
5.2.5.3 MediastinalLymphNodeStaging................................ 142
5.2.5.4 StagingofDistantMetastases ................................... 142
5.2.5.5 RecurrentLungCancer ........................................ 143
5.2.5.6 TherapyMonitoring ........................................... 143
5.2.6 SmallCellLungCancer ........................................ 144
Contents XI
5.2.7 MalignantPleuralMesothelioma ................................ 145
References .......................................................... 145
6 Liver,SpleenandBiliaryTree
L.S.Zuckier,L.M.Freeman ................................... 147
6.1 BriefIntroductionandHistoricalPerspective...................... 147
6.2 BiliaryExcretion .............................................. 147
6.2.1 Radiopharmaceuticals ......................................... 147
6.2.2 Methodology ................................................. 148
6.2.3 ClinicalIndicationsandInterpretation ........................... 149
6.2.3.1 DisordersofHepaticUptakeandExcretionintoBowel .............. 150
6.2.3.2 DisordersofGallbladderVisualization ........................... 151
6.2.3.3 FunctionalDisordersoftheGallbladder .......................... 152
6.2.3.4 Post-operativeandPost-traumaticPatients........................ 152
6.2.3.5 BiliaryAtresia ................................................ 154
6.2.3.6 CharacterizationofLiverMasses ................................ 155
6.3 ReticuloendothelialSystemImagingoftheLiverandSpleen ......... 156
6.3.1 Radiopharmaceuticals ......................................... 156
6.3.2 Methodology ................................................. 156
6.3.3 ClinicalIndicationsandInterpretation ........................... 157
6.3.3.1 DiffuseParenchymalDiseaseoftheLiver ......................... 157
6.3.3.2 FocalProcessesWithintheLiver ................................ 157
6.3.3.3 SplenicImaging............................................... 160
6.4 HemangiomaImaging ......................................... 161
6.4.1 Radiopharmaceuticals ......................................... 161
6.4.2 Methodology ................................................. 161
6.4.3 ClinicalIndicationsandInterpretation ........................... 161
6.5 18F-FluorodeoxyglucosePET .................................... 162
6.5.1 Introduction ................................................. 162
6.5.2 LiverMetastases .............................................. 162
6.5.3 BenignHepaticLesionsandHCC................................ 162
6.5.4 Cholangiocarcinoma .......................................... 163
6.5.5 GallbladderCarcinoma ........................................ 164
6.5.6 PancreaticMalignancy ......................................... 164
6.5.7 Artifacts ..................................................... 165
6.6 OtherAncillaryTechniques..................................... 165
6.6.1 HepaticArterialPerfusionScintigraphy .......................... 165
6.6.2 133XenonGas ................................................. 166
6.6.3 123I-and131I-Metaiodobenzylguanadine .......................... 166
6.6.4 111In-Octreotide............................................... 166
6.6.5 67Ga-Citrate .................................................. 166
6.6.6 ImmunologicImagingAgents................................... 167
6.7 SummaryandFutureDevelopments ............................. 168
References .......................................................... 168
7 Kidney
A.T.Taylor .................................................. 172
7.1 Radiopharmaceuticals ......................................... 172
7.1.1 Tc-99mDTPA(GlomerularFiltration)............................ 172
7.1.2 Cr-51EDTA(GlomerularFiltration) ............................. 172
7.1.3 I-123andI-131OIH(TubularSecretion).......................... 172
7.1.4 Tc-99mMAG3(TubularSecretion) .............................. 172
7.1.5 Tc-99mL,L-andD,D-EC(TubularSecretion)........................ 173
7.1.6 Tc-99mDMSA(CorticalRetention).............................. 173
7.1.7 Tc-99mGH(CorticalRetentionandGFR) ........................ 173
7.1.8 Tc-99mMDP(GFR) ........................................... 173
7.2 TechnicalIssuesandQualityControl ............................. 174
