Clinical Nuclear Medicine (eBook)

Preface 5
Contents 7
Part I: Basics 10
1: Physics, Instrumentation, and Radiation Safety and Regulations 11
1.1 Introduction 11
1.2 Basic Physics 11
1.2.1 Atomic and Nuclear Structure 11
1.2.2 Radioactivity 16
1.2.2.1 Nuclear Instability 16
1.2.2.2 Modes of Radioactive Decay 16
1.2.2.3 Mathematics of Radioactive Decay 17
1.2.3 Interactions of Radiation with Matter 19
1.2.3.1 Elastic and Inelastic Interactions 19
1.2.3.2 Photon (X- and ?-Ray) Interactions 19
1.2.3.3 Particulate-Radiation Interactions 21
1.3 Radiation Detection and Measurement 21
1.3.1 Statistical Considerations 21
1.3.2 Radiation Detector Performance 22
1.3.3 Basic Design and Operating Principles of Radiation Detectors 24
1.3.4 Ionization Detectors 24
1.3.5 Scintillation Detectors 26
1.3.6 Semiconductor-Based Ionization Detectors 28
1.4 Nuclear Medicine Instrumentation 28
1.4.1 Intraoperative Probes 28
1.4.2 Organ Uptake Probes 30
1.4.3 Gamma Cameras 30
1.4.4 Tomographic Scanners 32
1.4.4.1 Introduction 32
1.4.4.2 SPECT Data Acquisition 33
1.4.4.3 PET Data Acquisition 34
1.4.4.4 Data Processing and Tomographic Image Reconstruction 39
Normalization/Nonuniformity Correction 39
Dead Time Correction 39
Center-of-Rotation Misalignment Correction (SPECT) 39
Randoms Correction (PET) 41
Scatter Correction 41
Attenuation Correction 41
Image Reconstruction 42
Quantitation 42
1.4.4.5 Time-of-Flight (TOF) PET 43
1.4.5 Gamma Camera Performance and Quality Control 43
1.4.6 Multimodality Devices 47
1.5 Radiation Safety and Regulations 48
1.5.1 Quantities and Units 48
1.5.2 Regulatory Jurisdiction and Licensure 48
1.5.3 Sources of Radiation Exposure and Dose Limits 49
1.5.4 Personnel Dosimetry 50
1.5.5 Receipt, Transport, Storage, and Inventory of Radioactive Materials 51
1.5.6 Radiation Surveys 52
1.5.7 Waste Disposal 53
1.5.8 Emergency (i.e., Spill) Procedures 53
1.5.9 Release Criteria for Radionuclide Therapy 54
1.5.10 Record-Keeping 55
1.5.11 “Sensitive” Patient Populations 55
1.5.11.1 Pregnant Women 55
1.5.11.2 Nursing Mothers 55
1.5.11.3 Prospective parents 56
1.5.12 Concluding Remarks 56
References 56
2: Radiopharmaceutical Sciences 57
2.1 Introduction 57
2.2 Clinically Relevant Radionuclides 59
2.2.1 Introduction 59
2.2.2 Properties of Radionuclides for Medical Application 59
2.2.3 Nuclear Data 60
2.2.4 Reactor-Based Radionuclide Production 60
2.2.5 Accelerator-Based Radionuclide Production 61
2.2.6 Generator-Based Production of Radionuclides 62
2.2.7 High-Intensity ?-Ray Sources for Photonuclear Radionuclide Production 66
2.2.8 Spallation Neutron Sources for Radionuclide Production 67
2.2.9 Medical Applications of Radionuclides 67
2.2.10 Outlook on Future Radionuclides of Clinical Relevance 67
2.2.11 Radionuclides for Diagnosis and Therapy 68
2.2.11.1 The “Standard” PET Radionuclides 11C, 13N, 15O, and 18F 68
2.2.11.2 44gSc (T½ = 3.97 h) 69
2.2.11.3 52Mn (T½ = 5.591 Days) 70
2.2.11.4 64Cu (T½ = 12.7 h) 70
2.2.11.5 66Ga (T½ = 9.49 h) 71
2.2.11.6 67Ga (T½ = 3.2617 Days) 71
2.2.11.7 68Ga (T½ = 68.3 min) 72
2.2.11.8 72As (T½ = 26.0 h) 72
2.2.11.9 73Se (T½ = 7.1 h) 73
2.2.11.10 76Br (T½ = 16.2 h) 74
2.2.11.11 82mRb (T½ = 6.472 h) and 82Sr (T½ = 25.35 Days) 74
2.2.11.12 86Y (T½ = 14.7 h) 75
2.2.11.13 89Zr (T½ = 78.41 h) 75
2.2.11.14 90Y (T½ = 64.00 h) and 90Sr (T½ = 28.79 Years) 76
2.2.11.15 94mTc (T½ = 52.0 min) 76
2.2.11.16 99mTc (T½ = 6.0072 min) 76
2.2.11.17 111gIn (T½ = 2.8047 Days) 78
2.2.11.18 123I (T½ = 13.2235 h) and 124I (T½ = 4.18 Days) 78
2.2.11.19 125I (T½ = 59.407 Days) and 131I (T½ = 8.0252 Days) 79
2.2.11.20 147Gd (T½ = 38.06 h) 80
2.2.11.21 153Sm (T½ = 46.284 h) 80
2.2.11.22 177Lu (T½ = 6.647 Days) 80
2.2.11.23 186Re (T½ = 3.7183 Days) and 188Re (T½ = 17.0040 h) 81
2.2.11.24 193mPt (T½ = 4.3 Days) and 195mPt (T½ = 4.010 Days) 82
2.2.11.25 211At (T½ = 7.214 h) 82
2.2.11.26 225Ac (9.9203 Days) 82
2.2.11.27 223Ra (T½ = 11.43 Days) and 224Ra (T½ = 3.6319 Days) 83
2.3 Clinically Relevant SPECT Tracers 84
2.3.1 Technetium-99m (99mTc) 84
2.3.1.1 99Mo/99mTc-Generator 84
2.3.1.2 Basic Aspects of 99mTc- Radiopharmaceutical Chemistry 86
2.3.1.3 99mTc-Radiopharmaceuticals in Clinical Use 88
2.3.1.4 Inorganic99mTc- Compounds 89
Sodium [99mTc]pertechnetate 89
[99mTc]Tc2S7 ([99mTc]Technetium-Sulfur Colloid) 89
99mTc on Carbon as Aerosol ([99mTc]Technegas) 89
2.3.1.5 99mTc-Complexes 89
Imaging of Renal Excretion 89
Imaging of Myocardial Blood Flow 90
Imaging of Cerebral Blood Flow 91
Receptor-Specific Targeting for Measurement of the Dopamine Transporter (DAT) Density and Function 91
99mTc-Radiopharmaceuticals for Sentinel Lymph Node (SNL) Localization 92
2.3.1.6 Receptor-Targeted ­99m Tc- Radiopharmaceuticals Based on Bifunctional Chelators 92
99mTc-Tilmanocept 92
99mTc-Labeled Peptides and Peptidomimetics for SPECT Imaging 92
SPECT Imaging of Apoptosis 92
Imaging (Neo)angiogenesis with SPECT 95
Imaging the av?3 Integrin with RGD Peptide Analogs 96
2.3.2 Indium-111 (111In) 101
2.3.3 Iodine-123 (123I) 102
2.3.3.1 Metaiodobenzylguanidine (MIBG) 102
2.3.3.2 Receptor-Specific Agents for Measurement of Receptor or Transporter Density and Function in the Brain 103
2.4 Clinically Relevant Diagnostic Non-radiometal PET Tracers 104
2.4.1 Carbon-11 (11C) 104
2.4.1.1 Introduction 104
2.4.1.2 Basics in 11C-Chemistry 104
2.4.1.3 Reactions with [11C]CO2 105
2.4.1.4 11C-Methylation Reactions 105
2.4.1.5 Other 11C-Building Blocks 107
2.4.2 Nitrogen-13 (13N) and Oxygen-15 (15O) 107
2.4.2.1 Basics in 13N- and 15O-Chemistry 107
2.4.2.2 [13N]Ammonia 108
2.4.2.3 [15O]Water 108
2.4.3 Fluorine-18 (18F) 108
2.4.3.1 Introduction 108
2.4.3.2 Basics in 18F-Chemistry 108
2.4.3.3 Direct Electrophilic 18F-Fluorination 109
2.4.3.4 Nucleophilic 18F-Fluorination 111
2.4.3.5 Direct Aliphatic Nucleophilic 18F-Substitution 112
2.4.3.6 Direct Aromatic Nucleophilic 18F-Fluorination 113
2.4.3.7 Fluoride-Acceptor Chemistry 116
2.4.3.8 Indirect 18F-Labeling of Biomolecules via Prosthetic Groups 118
2.4.4 Iodine-124 (124I) 121
2.4.4.1 Introduction 121
2.4.4.2 Basics in 124I-Chemistry 121
2.4.5 Automation in 18F- and 11C-Chemistry 122
2.4.6 Important Clinically Relevant 11C-, 13N-, 15O-, and 18F-Radiopharmaceuticals 122
2.4.6.1 Tissue/Organ Perfusion/Cerebral Metabolic Rate for Oxygen 123
2.4.6.2 Metabolism 125
Glucose Metabolism 125
Fatty Acid Metabolism 125
Choline Metabolism 126
Bone Metabolism 126
2.4.6.3 DNA Synthesis 126
2.4.6.4 Hypoxia 127
2.4.6.5 Amino Acid Transport and Protein Synthesis 127
2.4.6.6 Gene Expression 128
Gene Imaging 128
Direct Gene Imaging 128
Indirect Gene Imaging 128
2.4.6.7 Aggregated Protein Target 129
Imaging of ?-Amyloid Plaques 129
Imaging of Tau/Synuclein 130
2.4.6.8 Apoptosis 130
2.4.6.9 Specific Target Interactions 130
Somatostatin Receptors (SSTR) 130
Estrogen Receptors 132
Integrin ?v?3 Receptor 132
Metalloproteases 133
2.4.6.10 Neurotransmitter Systems 133
Dopamine System 133
Dopamine Metabolism 134
Dopamine Transporters 134
Dopamine Receptors 134
Monoamine Oxidase (MAO) Inhibitors 134
2.5 Clinically Relevant Theranostic Radiotracers 135
2.5.1 Concept of Theranostics and Personalized Medicine 135
2.5.2 Theranostic Radioligands for Peptide Receptor Radionuclide Therapy (PRRT) 136
2.5.3 Somatostatin Receptor (SSTR) 138
2.5.3.1 Somatostatin Analogs (SSA) for Imaging and Treatment of Neuroendocrine Tumors (NETs) 139
2.5.4 Prostate-Specific Membrane Antigen (PSMA) (cf. Sect. 2.4) 142
2.5.4.1 PSMA Inhibitors for Imaging and Treatment of Prostate Cancer (PC) 142
2.5.4.2 PSMA-Targeted Antibodies for Imaging and Treatment of Prostate Cancer (PC) 148
2.5.5 Gastrin-Releasing Peptide Receptor (GRPr) Ligands for Imaging and Treatment of Cancer 148
2.5.6 Further Theranostic Concepts and Tracers of Clinical Relevance 149
2.5.7 Peptides and Peptidomimetics for SPECT Imaging with the Option to Be Used in Combination with Radiotracers for Radioligand Therapy RLT 151
2.5.7.1 Somatostatin Receptor SPECT Imaging with 99mTc Combined with Therapy (cf. Sects. 2.4.5.8.1 and 2.5.3) 152
2.5.7.2 SPECT Imaging with Gastrin/Cholecystokinin 2 (CCK2) Analogs (cf. Sect. 2.5.6) 152
2.5.7.3 Glucagon-Like Peptide-1 Analogs (cf. Sect. 2.5.6) 156
2.5.7.4 Neurotensin Peptide Analogs for SPECT Imaging 157
2.5.7.5 Bombesin Receptor for Imaging and Therapy 158
2.5.7.6 Small and Low-Molecular-Weight Molecules Targeting Prostate-Specific Membrane Antigen (PSMA) 158
123I- and 131I-Labeled PSMA Radioligands 160
99mTc-Labeled PSMA Radioligands 162
References 163
3: Radiomics as Applied in Precision Medicine 200
3.1 Introduction 200
3.2 Scientific Background 201
3.3 Methodology 205
3.4 Clinical Application and Impact of Radiomics 209
References 211
Part II: Diagnostic Nuclear Medicine 215
4: SPECT and PET of the Brain 216
4.1 SPECT and PET Brain Imaging in the Evaluation of Dementia 216
4.2 SPECT and PET Imaging of the Dopamine System in Movement Disorders 222
4.3 SPECT and PET Imaging in the Evaluation of Cerebrovascular Diseases 225
4.4 SPECT and PET Brain Imaging in the Evaluation of Brain Tumors 226
4.5 SPECT and PET Brain Imaging in the Evaluation of Seizure Disorders 227
4.6 SPECT and PET Imaging of the Dopamine System in Psychiatric Disorders 228
4.7 Radionuclide Cerebrospinal Fluid Flow Studies 229
4.8 Brain Death Scintigraphy 231
Appendix 232
Radiopharmaceutical Abbreviations 232
References 233
5: Clinical Applications of Nuclear Cardiology 237
5.1 Introduction 237
5.2 Historical Perspective of Nuclear Cardiology 237
5.3 Perfusion Imaging 238
5.3.1 Basic Concepts 238
5.3.2 Radiopharmaceuticals and Imaging Protocols 238
5.3.2.1 Thallium-201 239
5.3.2.2 Technetium-99m Radiotracers 241
5.3.2.3 Tc-99m Sestamibi and Tetrofosmin 241
5.3.2.4 Tc-99m Radiotracer Imaging Protocol Options 241
5.3.3 Perfusion Tracers and Protocols for PET 244
5.3.3.1 O-15 Water 245
5.3.3.2 N-13 Ammonia 245
5.3.3.3 Rubidium-82 246
5.3.3.4 F-18 Flurpiridaz 246
5.3.4 Pharmacologic Stress Agents and Protocols 247
5.3.4.1 Vasodilators 248
Mechanism of Action, Safety, and Efficacy 248
Pharmacologic Stress Protocols 249
5.3.4.2 Catecholamines 251
5.3.5 SPECT and PET Image Acquisition 252
5.3.5.1 ECG Gating 253
5.3.5.2 Attenuation Correction 254
5.3.5.3 Hybrid Imaging 254
5.3.6 Quality Control (QC) of the Images and Reporting 254
5.3.6.1 Quantitative Analysis of MPI 255
5.3.6.2 Absolute Quantification of Perfusion 255
5.3.6.3 Image Interpretation 255
5.3.6.4 Generating a Report 256
5.3.7 Clinical Indications 256
5.3.7.1 Diagnosis and Risk Stratification of CAD 256
5.3.7.2 Special Populations 257
Ethnic and Racial Differences 257
Women 257
Patients with LBBB/Pacemakers, Left Ventricular Hypertrophy, Nonspecific ST-T Wave Changes 257
Asymptomatic Patients 258
Patients with Diabetes 258
Patients with Chest Pain in ED 258
Patients Before and After Revascularization 258
Risk Assessment of Patients Before Noncardiac Surgery 259
5.4 Myocardial Viability 259
5.4.1 Basic Concepts 259
5.4.2 Nuclear Cardiology to Assess Viability 260
5.4.2.1 F18-Fluorodeoxyglucose (F-18 FDG) 260
Viability Protocol 260
5.4.3 Clinical Indications 261
5.4.3.1 Ischemic Cardiomyopathy 261
5.5 Assessment of Ventricular Function by Radionuclide Ventriculography 262
5.5.1 Equilibrium Radionuclide Angiocardiography (ERNA) 262
5.5.1.1 Technique 262
Radiopharmaceuticals and Red Blood Cell Labeling 262
Labeling Techniques 262
Instrumentation and Procedure 263
Exercise Studies 265
5.5.1.2 Clinical Indications 265
Assessment of LV Function 265
Detection of CAD 265
Monitoring Cardiotoxicity 265
5.5.2 First-Pass Radionuclide Angiography (FPRNA) 266
5.5.2.1 Instrumentation and Procedure 266
5.6 Neurocardiac Imaging 266
5.6.1 Basic Concepts of Neurocardiac Imaging 266
5.6.2 Imaging Myocardium Sympathetic Innervation 267
5.6.3 Clinical Indications 268
5.6.3.1 Heart Failure 268
5.6.3.2 Ischemic Heart Disease 268
5.7 Nuclear Techniques in the Management of Inflammatory, Infectious, and Infiltrative Heart Diseases 269
5.7.1 Sarcoidosis 269
5.7.2 Amyloidosis 270
5.7.2.1 Imaging Protocols for Transthyretin Cardiac Amyloidosis 272
5.7.3 Myocardial Infections and Endocarditis 273
References 274
6: Ventilation/Perfusion SPECT Imaging Diagnosing PE and Other Cardiopulmonary Diseases 281
6.1 Introduction 281
6.2 Diagnosing Pulmonary Embolism 281
6.3 Basic Principles of Pulmonary Embolism Diagnosis with V/P SPECT 282
6.4 Radiopharmaceuticals for V/P SPECT 283
6.4.1 Ventilation 283
6.4.2 Perfusion 284
6.5 Imaging Protocols 284
6.6 Reporting Findings 285
6.6.1 Ventilation/Perfusion Patterns 285
6.6.2 Criteria for Acute Pulmonary Embolism 286
6.6.3 Quantification of PE Extent 286
6.7 Follow-Up 286
6.8 Chronic Pulmonary Embolism 287
6.9 CTPA 288
6.10 Sensitivity and Specificity of V/P SPECT and CT in Diagnosis of PE 288
6.11 Pregnancy 289
6.12 Radiation Doses 289
6.13 Clinical Use of Hybrid V/P SPECT/CT 290
6.14 Role of Ventilation SPECT in Diagnosis of Other Lung Diseases 291
6.14.1 Chronic Obstructive Pulmonary Disease (COPD) 291
6.14.2 Pneumonia 293
6.14.3 Left Heart Failure 293
6.14.4 Preoperative Evaluation of Lung Function 293
6.15 Conclusion 294
References 295
7: Scintigraphy of the Liver, Spleen, and Biliary Tree 298
7.1 Brief Introduction and Historical Perspective 298
7.2 Biliary Excretion 298
7.2.1 Radiopharmaceuticals 299
7.2.2 Methodology 299
7.2.3 Clinical Indications and Interpretation 301
7.2.3.1 Disorders of Hepatic Uptake and Excretion into the Bowel 303
7.2.3.2 Disorders of Gallbladder Visualization 304
7.2.3.3 Functional Disorders of the Gallbladder [15] 305
7.2.3.4 Postoperative and Post-traumatic Patients 306
7.2.3.5 Biliary Atresia 307
7.2.3.6 Characterization of Liver Masses 310
7.3 Reticuloendothelial System Imaging of the Liver and Spleen 311
7.3.1 Radiopharmaceuticals 311
7.3.2 Methodology [36, 37] 311
7.3.3 Clinical Indications and Interpretation 312
7.3.3.1 Diffuse Parenchymal Disease of the Liver 312
7.3.3.2 Focal Processes within the Liver 313
7.3.3.3 Splenic Imaging 316
7.4 Hemangioma Imaging 317
7.4.1 Radiopharmaceuticals 317
7.4.2 Methodology [36, 37] 317
7.4.3 Clinical Indications and Interpretation 317
7.5 Other Ancillary Techniques 318
7.5.1 18F-Fluorodeoxyglucose PET 318
7.5.2 Hepatic Arterial Perfusion Scintigraphy [37, 72] 318
7.5.3 133Xenon Gas 319
7.5.4 123I- and 131I-Metaiodobenzylguanadine 319
7.5.5 111In-Octreotide (Octreoscan) and 68Ga-DOTATATE 319
7.5.6 67Ga-Citrate 320
7.6 Summary and Future Developments 320
References 321
8: Nuclear Medicine Imaging Techniques of the Kidney 325
8.1 Radiopharmaceuticals 325
8.1.1 99mTc-DTPA (Glomerular Filtration) 325
8.1.2 51Cr-EDTA (Glomerular Filtration) 325
8.1.3 123I- and 131I-OIH (Tubular Secretion) 325
8.1.4 99mTc-MAG3 (Tubular Secretion) 326
8.1.5 99mTc-L,L and D,D-EC (Tubular Secretion) 326
8.1.6 99mTc-(CO3) NTA (Tubular Secretion) 327
8.1.7 Tc-99m DMSA (Cortical Retention) 327
8.1.8 Tc-99m GH (Cortical Retention and GFR) 327
8.1.9 99mTc-MDP (GFR) 327
8.2 Technical Issues and Quality Control 327
8.2.1 Patient Information 327
8.2.2 Administered Dose 327
8.2.3 Hydration 328
8.2.4 Image Over the Injection Site 328
8.2.5 Minimizing the Radiation Dose to the Patient 329
8.2.6 Postvoid Images of the Kidneys 329
8.3 Quantitative Measurements 329
8.3.1 Relative Uptake 329
8.3.2 Whole-Kidney Versus Cortical Regions of Interest (ROIs) 330
8.3.3 Time to Peak Height 330
8.3.4 Twenty Min/Maximum Count Ratios 330
8.3.5 Prevoid/Maximum, Postvoid/Maximum, Prevoid/1–2 Min, and Postvoid/1–2 Min Count Ratios 331
8.3.6 Residual Urine Volume 331
8.4 Renal Function 332
8.4.1 Plasma Sample Clearances 332
8.4.2 Camera-Based Clearances 332
8.5 Renal Transplantation 333
8.6 Diuresis Renography 334
8.6.1 Technical Issues Relating to Diuresis Renography 334
8.6.1.1 Pretest Voiding 334
8.6.1.2 Choice of Radiopharmaceutical 334
8.6.1.3 Hydration 334
8.6.1.4 Dose of Furosemide 334
8.6.1.5 Timing of Furosemide Administration 338
8.6.1.6 Patient Position 338
8.6.1.7 Postvoid Images 339
8.6.1.8 Region of Interest (ROI) Selection for the Diuretic Portion of the Study 339
8.6.1.9 Calculating the T½ 339
8.6.1.10 Adequacy of Diuresis 340
8.6.2 Interpretation 340
8.6.2.1 Interpreting the T½ 340
8.6.2.2 Alternatives to the T½ 340
8.6.2.3 Relative Function 340
8.6.2.4 Nondiagnostic Studies 341
8.6.3 Diuresis Renography in Acute Renal Colic 341
8.7 Renovascular Hypertension and ACE Inhibition Renography 341
8.7.1 Pathophysiology of Renovascular Hypertension and ACE Inhibition 342
8.7.2 Technical Issues Relating to ACE Inhibition Renography 344
8.7.2.1 Diet and Hydration 344
8.7.2.2 Medications 345
8.7.2.3 Choice of Radiopharmaceutical 345
8.7.2.4 Choice of ACE Inhibitor 345
8.7.2.5 Blood Pressure 345
8.7.2.6 1- Versus a 2-Day Protocol 349
8.7.2.7 Furosemide-Augmented ACEI Renography 349
8.7.3 Diagnostic Criteria 349
8.7.4 Sensitivity and Specificity 350
8.7.4.1 Hypertensive Patients with Azotemic Renovascular Disease (ARVD) 350
8.7.4.2 Hypertensive Patients Without Azotemic Renovascular Disease (ARVD) 351
8.8 The Role of Positron Emission Tomography in Renal Imaging 351
8.8.1 PET Applications in Renal Cell Carcinoma (RCC) 352
References 353
9: Nuclear Medicine Imaging Techniques of the Gastrointestinal System 358
9.1 Introduction 358
9.2 Gastric Emptying 358
9.3 Clinical Presentation 359
9.4 Standardized Gastric Emptying Scintigraphy 359
9.5 Liquid Gastric Emptying 364
9.6 Gastric Accommodation Scintigraphy 366
9.7 Intestinal Transit Scintigraphy 367
9.8 Esophageal Transit Scintigraphy 370
9.9 Gastroesophageal Reflux Disease (GERD) 372
9.10 Gastrointestinal Bleeding Scintigraphy 374
9.11 Meckel’s Scan 377
References 379
10: Nuclear Medicine Imaging Techniques of the Musculoskeletal System 382
10.1 Introduction 382
10.2 Radiopharmaceuticals and Mechanisms of Uptake 384
10.3 Scintigraphy Techniques 384
10.4 Scintigraphic Patterns, Variants and Artefacts 386
10.5 Clinical Application of Bone Scans in Specific Cancers 390
10.5.1 Breast Cancer 390
10.5.2 Prostate Cancer 390
10.5.3 Other Genitourinary Tumours 392
10.5.4 Lung Cancer 392
10.5.5 Neuroblastoma 393
10.5.6 Miscellaneous Tumours 394
10.6 Clinical Applications of Bone Scan in Metabolic Bone Disease 395
10.6.1 Osteoporosis 395
10.6.2 Paget’s Disease 397
10.6.3 Hyperparathyroidism 398
10.6.4 Renal Osteodystrophy 399
10.6.5 Osteomalacia 400
10.7 Clinical Application of Bone Scans in Sports-/Exercise-Related Injuries 400
10.8 Clinical Applications of Bone Scan in Infection and Evaluation of Joint Prostheses 401
10.9 Clinical Application of Bone SPECT 406
10.10 Bone SPECT/CT in Skeletal Disease 410
10.10.1 Orthopaedics: Pre- and Postoperative Scenario 410
10.10.2 Bone SPECT/CT in Oncology 412
10.11 Positron Emission Tomography (PET) in Skeletal Disease 414
References 426
11: Application of Lymphatic Mapping and Sentinel Node Biopsy in Surgical Oncology 432
11.1 Brief Introduction and Historical Perspective 432
11.2 General Aspects of Sentinel Node Mapping in Surgical Oncology 434
11.2.1 Radiopharmaceuticals 434
11.2.2 Injection Site, Time, Dose, and Volume 434
11.2.3 Lymphoscintigraphy 436
11.2.4 Intraoperative Gamma Probes and Issues to Be Considered during Surgery 439
11.2.5 Sentinel Node Algorithm and Problem of Midline Tumors 441
11.3 Breast Cancer 441
11.4 Melanoma 442
11.5 Uterine Cervix Cancer 444
11.6 Endometrial Cancer 445
11.7 Vulvar Cancer 448
11.8 Penile Cancer 449
11.9 Colorectal Cancer 450
11.10 Head and Neck Cancers 453
11.11 Other Solid Tumors 454
References 455
12: Lymphoscintigraphy in the Management of Lymphatic Disorders 460
12.1 Brief Introduction and Historical Perspective 460
12.2 Radiopharmaceuticals 460
12.3 Methodology 461
12.3.1 Prestudy Preparations 461
12.3.2 Injection Technique 461
12.3.2.1 Radiotracer Dose 461
12.3.2.2 Injection Site and Numbers 461
12.3.3 Exercise Following Radiotracer Injections 462
12.3.4 Imaging 463
12.4 Clinical Indications and Interpretation 464
12.4.1 Differentiation of Lymphedema From Other Causes of Limb Swelling 464
12.4.1.1 Qualitative Criteria of Lymphedema 464
12.4.1.2 Semi-quantitative Approach of Image Interpretation 465
Inguinal/Axillary to Injection Site Uptake Ratio 465
Radiotracer Removal Constant Rates Based on Dynamic Imaging 468
12.4.1.3 Normal-Appearing Limbs and Lymphoscintigraphy Abnormalities 470
12.4.2 Localization of Lymphatic System Defects 470
12.4.3 Follow-Up of Patients With Lymphatic System Disorders 470
12.4.4 Prediction of the Development of Lymphedema 470
References 477
13: Nuclear Medicine Imaging Techniques of the Neuroendocrine System 480
13.1 Neuroendocrine Tumors 480
13.1.1 Primary Diagnosis 481
13.1.2 Therapy Management 482
13.1.3 Therapy Monitoring 482
13.1.4 Diagnosis of Recurrence 484
13.1.5 SSTR PET/MRI 484
13.1.6 SSR Antagonists 484
13.1.7 Neuroendocrine Carcinoma 484
13.1.8 Pheochromocytoma and Paraganglioma 485
13.2 Neuroblastoma 486
13.3 Medullary Thyroid Cancer 486
References 487
14: Thyroid and Parathyroid Imaging 490
14.1 Thyroid 490
14.1.1 Thyroid Embryology, Anatomy and Physiology 490
14.1.2 Thyroid Hormone Synthesis 492
14.1.3 The Thyroid Examination 493
14.1.3.1 Radiopharmaceuticals 493
14.1.3.2 Thyroid Scintigraphy 494
14.1.3.3 Radioactive Iodine Uptake 495
14.1.4 Normal Thyroid Scintigraphy 496
14.1.5 Abnormal Thyroid 496
14.1.5.1 Congenital Abnormalities and Hypothyroidism 496
14.1.5.2 Hyperthyroidism 496
Graves’ Disease 498
Thyroid Nodules 498
Thyroiditis 500
Amiodarone Induced Thyrotoxicosis 501
14.2 Parathyroid 501
14.2.1 Parathyroid Embryology, Anatomy and Physiology 501
14.2.2 Hyperparathyroidism 502
14.2.2.1 Primary Hyperparathyroidism 502
14.2.2.2 Parathyroid Imaging 503
Historical Evolution 503
Dual-Isotope Imaging 504
Dual-Phase Imaging 504
Pitfalls of Dual-Phase Imaging 505
SPECT/CT 506
Image Interpretation 506
14.2.2.3 Secondary Hyperparathyroidism 507
14.2.2.4 Tertiary Hyperparathyroidism 507
14.2.3 PET/CT 508
References 508
15: Molecular Imaging of Inflammation and Infection 512
15.1 Introduction 512
15.2 Single-Photon-Emitting Radiopharmaceuticals 512
15.2.1 Gallium-67 Citrate 512
15.3 Labeled Leukocytes 515
15.3.1 In Vivo Labeled Leukocytes 523
15.4 Positron-Emitting Radiopharmaceuticals 523
15.5 18F-Fluorodeoxyglucose 525
15.6 Other Positron-Emitting Radiopharmaceuticals 531
15.7 Infection-Specific Agents 531
15.7.1 Radiolabeled Antibiotics 531
15.7.2 111In-Biotin 531
15.7.3 Radiolabeled Antimicrobial Peptides 532
15.8 Summary 532
References 532
16: Imaging of Atherosclerosis with 18F-FDG PET 538
16.1 Introduction 538
16.2 Methodology 539
16.3 Arterial FDG PET Imaging in Clinical Studies 541
16.4 Correlation with Clinical Cardiovascular Risk Factors 542
16.5 Prognostic Value of Arterial FDG PET Imaging on Cardiovascular-Related Outcome 542
16.6 FDG PET as a Surrogate Endpoint Marker in Clinical Interventional Trials 544
16.7 New Approaches in Imaging Atherosclerosis with PET 545
References 546
17: PET/CT and PET/MRI, Normal Variations, and Artifacts 549
17.1 Technical Artifacts 549
17.1.1 Partial Volume Effect 549
17.1.2 Motion Artifacts 549
17.1.3 Artifacts Induced by High-Density Materials 550
17.1.4 Truncation Artifact 551
17.1.5 Equipment Errors Causing Artifacts 551
17.2 PET/MRI 551
17.3 18F-FDG 552
17.3.1 Head and Neck 552
17.3.2 Chest 554
17.3.3 Abdomen 558
17.3.4 Pelvis 559
17.3.5 Brain 561
17.4 11C- and 18F-Choline 563
17.4.1 Brain/Head and Neck 563
17.4.2 Thorax 564
17.4.3 Abdomen 565
17.4.4 Pelvis/Genitourinary System 565
17.4.5 Treatment Effect 566
17.5 11C-Acetate 566
17.5.1 Brain/Head and Neck 566
17.5.2 Thorax 566
17.5.3 Abdomen 566
17.5.4 Pelvis 567
17.6 18F-DOPA 568
17.6.1 CNS: Head and Neck 568
17.6.2 Thorax 568
17.6.3 Abdomen 568
17.6.4 Effect of Carbidopa Premedication on the Biodistribution of 18F-DOPA 569
17.7 68Ga-DOTA-Peptides 569
17.7.1 Brain / Head and Neck 570
17.7.2 Thorax 570
17.7.3 Abdomen 570
17.7.4 Pelvis 570
17.7.5 Effects of Aging and Treatment 571
17.8 68Ga-PSMA 571
17.8.1 Head and Neck 572
17.8.2 Thorax 572
17.8.3 Abdomen 572
17.8.4 Pelvis 572
17.8.5 Effects of Aging and Treatment 573
17.9 18F-FLT 573
17.9.1 Brain/Head and Neck 573
17.9.2 Thorax 574
17.9.3 Abdomen 574
17.9.4 Pelvis 575
17.9.5 Effects of Aging and Treatment 575
17.9.5.1 Aging 575
17.9.5.2 Treatment-Induced Effects 575
17.10 18F-NaF 575
References 577
18: PET in Head and Neck Cancer 585
18.1 Introduction 585
18.2 Initial Staging of Head and Neck Cancer 585
18.3 Therapy Response and Residual Tumor Detection 586
18.4 Restaging in Recurrent Disease and Second Malignancies 588
18.5 Thyroid Cancer 588
18.6 124I PET 589
18.7 FDG PET 589
18.8 Cancer of Unknown Primary (CUP) 590
18.9 PET/CT vs. PET/MRI 590
18.10 Pitfalls 591
18.11 Examples for PET/CT and PET/MR Protocols for Head and Neck Cancer 592
18.11.1 PET/CT 592
18.11.1.1 Neck 592
18.11.1.2 Whole Body 592
18.11.1.3 Thorax 592
18.11.2 PET/MRI 592
References 593
19: PET in Gastrointestinal, Pancreatic, and Liver Cancers 597
19.1 Esophageal Cancer 597
19.1.1 Diagnosis and Staging 597
19.1.2 Recurrence/Restaging 598
19.1.3 Prognosis/Response to Treatment 598
19.2 Gastric Cancer 599
19.2.1 Diagnosis and Staging 600
19.2.2 Recurrence/Restaging 600
19.2.3 Prognosis/Response to Treatment 600
19.3 Gastrointestinal Stroma Cell Tumors (GISTs) 601
19.4 Colorectal Cancer 602
19.4.1 Diagnosis and Staging 602
19.4.2 Recurrence/Restaging 604
19.4.3 Prognosis/Response to Treatment 605
19.5 Pancreatic Cancer 606
19.5.1 Diagnosis and Staging 606
19.5.2 Recurrence/Restaging 608
19.5.3 Prognosis/Response to Treatment 608
19.6 Liver Cancer 609
19.7 Conclusion 610
References 611
20: 18F-FDG-PET/CT in Breast and Gynecologic Cancer 626
20.1 Breast Cancer 626
20.1.1 Epidemiology 626
20.1.2 Breast Cancer Detection, Diagnosis, and Staging 627
20.1.3 Role of 18F-FDG-PET/CT in Staging Large or Locally Advanced Breast Cancer 628
20.1.4 Role of FDG-PET/CT in Staging of Distant Metastatic Breast Cancer 630
20.1.5 Role of 18F-FDG-PET/CT in Evaluating Response to Treatment in Breast Cancer 632
20.1.6 Novel Radiotracers 633
20.2 Ovarian Cancer 635
20.2.1 Epidemiology 635
20.2.2 Ovarian Cancer Detection and Diagnosis 635
20.2.3 Role of 18F-FDG-PET/CT in the Primary Diagnosis of Ovarian Cancer 636
20.2.4 Role of 18F-FDG-PET/CT in Ovarian Cancer Staging 636
20.2.5 Role of 18F-FDG-PET/CT in the Response to Treatment of Ovarian Cancer 637
20.2.6 Role of 18F-FDG-PET/CT in Recurrent Ovarian Cancer 638
20.2.7 Novel Radiotracers in Ovarian Cancer 638
20.3 Endometrial Cancer 638
20.3.1 Epidemiology 638
20.3.2 Endometrial Cancer Detection, Diagnosis, and Staging 639
20.3.3 Role of 18F-FDG-PET/CT in Evaluating Treatment Response in Endometrial Cancer 640
20.3.4 Novel Radiotracers in Endometrial Cancer Imaging 640
20.4 Cervical Cancer 641
20.4.1 Epidemiology, Detection, and Diagnosis 641
20.4.2 Cervical Cancer Staging 641
20.4.3 PET/CT in the Evaluation of the Response to Treatment of Cervical Cancer 643
20.4.4 Novel Radiotracers 643
20.4.5 PET/MRI 644
References 644
21: PET in Lung Cancer and Mediastinal Malignancies 650
21.1 Lung Cancer 650
21.1.1 Solitary Pulmonary Nodules 650
21.1.2 NSCLC Primary Staging 652
21.1.3 SCLC Primary Staging 656
21.1.4 Recurrence of NSCLC 656
21.2 Malignant Pleural Effusion 658
21.3 Pleural Mesothelioma 658
21.4 Thymic Epithelial Tumors (TETs): Thymoma and Thymic Carcinoma 660
References 662
22: Nuclear Medicine Imaging Techniques in Melanoma 664
22.1 Introduction 664
22.2 Morphology 664
22.3 Prognostic Factors 665
22.4 Sentinel Lymph Node Scintigraphy 665
22.4.1 Radiopharmaceuticals 667
22.4.2 Methodology 669
22.4.2.1 Patient Preparation 669
22.4.2.2 Injection Technique 669
22.4.3 Preoperative Imaging 669
22.4.3.1 Dynamic Imaging 669
22.4.3.2 Static Images 670
22.4.3.3 SPECT and SPECT/CT Imaging 670
22.4.4 Intraoperative Procedure 670
22.4.5 Indications and Contraindications 670
22.5 18F-FDG PET/CT Imaging of Melanoma 671
22.5.1 Staging 671
22.5.2 Therapy Response Assessment 671
22.5.3 Surveillance 674
22.6 Tracers for Specific Targeting of Melanoma 678
References 679
23: PET in Lymphoma 683
23.1 Introduction 683
23.2 Classification and Staging 685
23.3 Imaging for Staging in Lymphoma 687
23.3.1 International Prognostic Index (IPI) and Score (IPS) 688
23.4 Clinically Relevant Issues About Lymphomas 689
23.5 18F-FDG PET/CT in Initial Staging of Lymphoma 690
23.5.1 Bone Marrow Involvement 692
23.5.2 Spleen Involvement 694
23.5.3 Liver Involvement 696
23.6 PET/CT Response Assessment 697
23.6.1 Hodgkin Disease 697
23.6.2 Diffuse Large B-Cell Lymphoma (DLBCL) 698
23.6.3 Other Lymphomas 698
23.6.3.1 Follicular Lymphoma 698
23.6.4 T-Cell Lymphoma 699
23.6.5 Mantle Cell Lymphoma 701
23.6.6 Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma 701
23.6.7 Marginal Zone Lymphomas 703
23.6.8 Posttransplant Lymphoproliferative Disorders 703
23.6.9 FDG-PET in Extranodal Lymphoma 703
23.7 Response Assessment Criteria on FDG PET/CT 708
23.7.1 Response Evaluation Methods 709
23.7.1.1 Eligible Lesions 710
23.7.1.2 Selection of Lesions 710
23.7.2 Response Categories Based on Assessment of Target Lesions 710
23.7.3 Disease Progression After Initial Response 711
23.7.3.1 Response Assessment to Immune-Modulating Agents, Including Checkpoint Inhibitors 711
23.7.4 Appearance of New Extranodal Lesion 711
23.7.5 Quantification of Treatment Response with FDG PET/CT 711
23.8 Pitfalls in Lymphoma Imaging 712
23.8.1 Sarcoid-Like Granulomas 712
23.8.2 Benign Lymphoproliferative Disorders 712
23.8.3 Other Nonspecific Lymphadenopathies 712
23.8.4 Thymic Uptake 714
23.8.5 BM Uptake After Administration of Colony Stimulators 714
23.8.6 Posttransplantation Period 714
23.8.7 AIDS-Related Lymphoma 715
23.9 Conclusions 716
References 717
24: PET/CT in Renal, Bladder, and Testicular Cancer 728
24.1 Introduction 729
24.2 Use of PET in Renal Cell Carcinoma 729
24.2.1 Overview of RCC 729
24.2.2 Primary RCC 729
24.2.3 Staging of RCC 732
24.2.4 Metastatic RCC 732
24.2.5 Other Agents for RCC 732
24.2.6 Summary 734
24.3 Use of PET in Bladder Cancer 735
24.3.1 Overview of Bladder Cancer 735
24.3.2 Primary Bladder Cancer 735
24.3.3 Staging 736
24.3.4 Restaging 738
24.3.5 Response to Therapy 739
24.3.6 Prognostic Value 740
24.3.7 Other Agents for Bladder Cancer 740
24.3.8 Pelvic and Ureter Cancer 741
24.3.9 Summary 741
24.4 Use of PET in Testicular Cancer 741
24.4.1 Overview of Testicular Cancer 741
24.4.2 Primary Testicular Cancer 742
24.4.3 Staging 742
24.4.4 Residual Disease 743
24.4.4.1 Other Agents for Testicular Cancer 745
24.4.5 Summary 745
References 745
25: PSMA-Ligand Imaging in the Diagnosis of Prostate Cancer 752
25.1 Physiologic Distribution of PSMA-Ligands 752
25.2 Lesion Characteristics for Prostate Cancer 753
25.3 Imaging Recurrent Prostate Cancer 753
25.4 Impact of Different Factors on PSMA-Ligand PET/CT in Recurrent Prostate Cancer 757
25.5 Imaging Timing After Application 757
25.6 Imaging Primary Prostate Cancer and Primary Staging of Prostate Cancer 757
25.7 Other Indications of PSMA-Ligand Imaging 758
References 759
26: Lacrimal Dacryoscintigraphy, Radionuclide Hysterosalpingography, and Scrotal Scintigraphy 761
26.1 Lacrimal Dacryoscintigraphy 761
26.2 Radionuclide Hysterosalpingography 762
26.3 Scrotal Scintigraphy 763
References 764
27: Radionuclide Imaging of Children 766
27.1 Introduction 766
27.2 Genitourinary System 766
27.3 Dynamic Renography 767
27.4 Renal Cortical Imaging 770
27.5 Radionuclide Cystography 771
27.6 Gastric Emptying 774
27.7 Pulmonary Aspiration 776
27.8 Gastroesophageal Reflux Study 777
27.9 Meckel’s Diverticulum Scan 777
27.10 Hepatobiliary Scan 781
27.11 Bone Scintigraphy 784
27.12 MIBG Scan 793
27.13 18F-FDG PET/CT 794
27.14 PET/MR 797
27.15 Brain Scintigraphy for Brain Death 797
27.16 Ventilation/Perfusion Scans for Pulmonary Embolism 800
27.17 Thyroid Scan for Congenital Hypothyroidism 802
References 805
Part III: Nuclear Medicine Therapy 808
28: Radioiodine Therapy for Benign Thyroid Disease 809
28.1 Introduction 809
28.2 Treatment Options for Hyperthyroidism and Nontoxic Goiter 810
28.3 Physical and Radiobiological Properties of Radioiodine 811
28.4 Contraindication for Radioiodine Therapy and Precautions 812
28.4.1 Pregnancy and Breast Feeding 812
28.4.2 Uncontrolled Hyperthyroidism 813
28.4.3 Tracheal Stenosis 813
28.4.4 Hypersensitivity 814
28.5 Procedure 814
28.5.1 Facility and Legislation 814
28.5.2 Patient Preparation 814
28.5.3 Special Considerations for Medication 815
28.6 Patient Information and Instruction 816
28.7 Radiation Dosimetry and I-131 Activity 816
28.8 Side Effects of I-131 Therapy 818
28.8.1 Acute Side Effects 818
28.8.2 Hypothyroidism 818
28.8.3 Autoimmune Thyroiditis 819
28.8.4 Radiation-Induced Cancers 819
28.9 Success Rate 819
28.9.1 Toxic Multinodular Goiter 819
28.9.2 Solitary Hyperfunctioning Nodule 819
28.9.3 Nontoxic Multinodular Goiter 819
28.9.4 Graves’ Disease 820
28.10 Follow-Up After Radioiodine Treatment 820
References 821
29: Differentiated Thyroid Cancer: Radioiodine Therapy 824
29.1 Introduction 824
29.1.1 Historical Perspective 824
29.1.2 Differentiated Thyroid Cancer 824
29.1.2.1 Incidence 825
29.1.2.2 Histology and Clinical Behaviour 825
PTC 825
FTC 825
29.1.2.3 DTC Treatment 825
Surgery 825
Thyroid Hormone Replacement Therapy 827
Radioiodine (I-131) Therapy 827
The Effectivity of Radioiodine Therapy 827
Practical Considerations 827
29.1.2.4 A Short How-to 829
Low-Iodine Diet 829
Pre-ablation Uptake Measurement/Scanning 829
rhTSH Stimulation 829
I-131 Activities 830
I-131 Therapy of Advanced DTC and Dosimetry 830
29.2 Side Effects and Complications 832
29.3 Conclusion 832
References 832
30: Palliation of Metastatic Bone Pain with Radiolabeled Phosphonates 838
30.1 Introduction 838
30.2 Radiolabeled Phosphonates in the Treatment of Bone Pain 839
30.2.1 Samarium-153 EDTMP 839
30.2.1.1 Samarium-153 EDTMP Binding Mechanism and Biodistribution 839
30.2.1.2 Samarium-153 EDTMP Single-Dose Treatment 840
30.2.1.3 Samarium-153 EDTMP Repeated Sequential Treatment 841
30.2.1.4 Samarium-153 EDTMP Combined with Chemotherapy 842
30.2.1.5 Samarium-153 EDTMP Combined with External Beam Radiotherapy 842
30.2.1.6 Samarium-153 EDTMP Combined with Bisphosphonates 843
30.2.2 Rhenium-188 HEDP 844
30.2.3 Lutetium-177 EDTMP 845
30.3 Conclusion 845
References 846
31: Radionuclide Therapy of Bone Metastases with Radium-223 Chloride in Prostate Cancer Patients 850
31.1 Introduction 850
31.2 Physical Characteristics 851
31.3 Uptake Mechanism and Biodistribution 853
31.4 Dosimetry 853
31.5 Pain Documentation 854
31.6 Clinical Indications 854
31.7 Effects of Therapy 855
31.8 Side Effects 856
31.9 Protocol of Application 857
31.10 Patient Preparation 857
References 858
32: Peptide Receptor Radionuclide Therapy 860
32.1 Introduction 860
32.2 Radiopharmaceuticals 860
32.2.1 Somatostatin Receptor Targeting 861
32.2.1.1 Somatostatin Receptors as Targets 861
32.2.1.2 Somatostatin Analogues 862
32.2.2 Isotopes 862
32.2.2.1 Indium-111 862
32.2.2.2 Lutetium-177 and Yttrium-90 863
32.2.2.3 Bismuth-213 863
32.2.2.4 Actinium-225 864
32.3 Rationale and Patient Selection 864
32.3.1 When to Start with PRRT? 864
32.3.2 Inclusion and Exclusion Criteria 864
32.3.3 Dual Molecular Imaging for Better Patient Selection 865
32.4 Applications 867
32.4.1 PPRT as a Palliative Treatment 867
32.4.2 Recommendations in the Guidelines 867
32.4.2.1 The ENETS Guidelines 867
32.4.2.2 The NANETS Guidelines 868
32.4.2.3 The NCCN Guidelines 869
32.4.3 Neoadjuvant Treatment with PRRT 869
32.4.4 Rare Indications 870
32.4.4.1 Phaeochromocytoma and Paraganglioma 870
32.4.4.2 Medullary Thyroid Cancer and Non-iodine Avid Differentiated (Nonmedullary) Thyroid Cancer 870
32.5 Patient Preparations and Administration 871
32.5.1 Discontinuation of Other Somatostatin Analogues 871
32.5.2 Amino Acid Administration for the Renal Protection 871
32.5.3 Administration of PRRT 872
32.5.4 Intravenously Vs Intrarterial Administration 872
32.6 Efficacy 873
32.6.1 Efficacy of PPRT in Comparison to Other Systemic Treatments 873
32.6.2 Efficacy of PRRT in Different Types of Neuroendocrine Tumours 874
32.6.3 Predictive Factors for Efficacy 874
32.6.4 Efficacy of PRRT as Single Agent 875
32.6.4.1 [177Lu]Lu-Octreotate: The First Widely Approved Agent 875
32.6.4.2 Efficacy and Safety of [177Lu]Lu-Edotreotide in GEP-NET Patients 875
32.6.4.3 Studies with [90Y]Y-Octreotide 876
32.6.4.4 Treatment with [90Y]Y-Octreotate 876
32.6.5 Combination of Lutetium-177 and Yttrium-90-Labelled PRRT 877
32.6.6 Combination Therapies of PRRT with Other Systemic Therapies 877
32.6.6.1 PRRT and Somatostatin Analogues 877
32.6.6.2 PRRT and Chemotherapy 878
32.6.6.3 Combination with Everolimus 879
32.6.7 Re-challenge PRRT 879
32.7 Toxicity 880
32.7.1 Definition of Toxicity 880
32.7.2 Acute Toxicity 881
32.7.3 Subacute Toxicity 881
32.7.4 Delayed Toxicity 881
32.8 Dosimetry 882
32.8.1 Tumour Dosimetry 882
32.8.2 Kidney Dosimetry 882
32.8.3 Bone Marrow Dosimetry 883
32.8.4 Dosimetry of Other Organs 883
32.9 Quality of Life 883
32.10 Controls After PRRT Administration and Follow-Up 883
32.11 New Development: PRRT with Antagonists 884
32.12 Conclusion and Future Developments 886
References 886
33: Treatment of Neuroendocrine Tumours (Neuroblastoma Stage III or IV, Metastatic Pheochromocytoma, Etc.) with 131I-mIBG 892
33.1 History 892
33.1.1 The Radiopharmaceutical mIBG 892
33.1.2 MIBG Uptake Mechanisms 893
33.1.3 Physiologic Distribution 893
33.1.4 Pitfalls 893
33.2 Indications for 131I-mIBG Therapy 893
33.2.1 Neuroblastoma Stage III or IV 893
33.2.2 Metastatic Pheochromocytoma/Paraganglioma (Extraadrenal Pheochromocytoma) 894
33.2.3 Rare Indications (Metastatic Carcinoid Tumours, mMTC, mMCC) 894
33.3 Contraindications for 131I-mIBG Therapy 897
33.4 Patient Preparation for 131I-mIBG 897
33.4.1 Interfering Medications 897
33.4.2 Thyroid Protection 897
33.4.3 Practical Aspects 897
33.5 Radionuclide Dosage and Results 899
33.5.1 Diagnostic Imaging 899
33.5.2 Dosage and Results of 131I-mIBG Treatment 899
33.5.2.1 Neuroblastoma Stage III or IV 899
33.5.2.2 Metastatic Pheochromocytoma/Paraganglioma (Extraadrenal Pheochromocytoma) 900
33.5.2.3 Rare Indications 900
33.6 Complications/Side Effects of 131I-mIBG Therapy 901
33.7 Image Acquisition 902
33.8 Radiation Exposure/Dosimetry 902
33.9 Potential Future Developments 903
References 904
34: Radioimmunotherapy 909
34.1 Introduction 909
34.2 Radiopharmaceuticals for Radioimmunotherapy 910
34.2.1 Development and Manufacture of mAbs 910
34.2.2 Radioimmunoconjugation for RIT 911
34.3 Different Strategies for RIT 913
34.3.1 Factors to Be Considered for Developing an Effective RIT Strategy 913
34.3.2 Pretargeting Strategies 914
34.3.2.1 Proof of Concept of DOTA-PRIT: A Platform Approach in Human Tumors 915
34.3.3 Combination Therapy 915
34.3.4 Dosimetry for RIT 915
34.3.5 Nonmyeloablative vs Myeloablative RIT 915
34.3.6 Dosing Methods for RIT 916
34.3.7 Immuno-PET 916
34.3.8 RIT vs Immunotherapy 916
34.4 Clinical Studies 916
34.4.1 Hematopoietic Tumors 917
34.4.1.1 B-Cell Non-Hodgkin’s Lymphoma 917
34.4.1.2 90Y-Ibritumomab Tiuxetan (Zevalin) 918
34.4.1.3 Dosimetry and Dosing 918
34.4.1.4 Preparation and Administration 918
34.4.1.5 Adverse Effects and Toxicity 919
34.4.1.6 Radiation Safety Measures 919
34.4.1.7 131I-Tositumomab (Bexxar) 919
34.4.1.8 Dosimetry and Dosing 919
34.4.1.9 Preparation and Administration 919
34.4.1.10 Adverse Effects and Toxicity 920
34.4.1.11 Radiation Safety Measures 920
34.4.1.12 Clinical Experience of Radioimmunotherapy in B-Cell NHL 920
34.4.1.13 RIT in Relapsed/Refractory B-Cell NHL or Transformed Lymphoma 922
34.4.1.14 RIT Following Failure of Rituximab 922
34.4.1.15 First-Line Therapy 922
34.4.1.16 Results of Phase II Myeloablative Dose of RIT 923
34.4.1.17 RIT Combined with Chemotherapy 923
34.4.1.18 Summary of RIT in B-Cell NHL 923
34.4.1.19 RIT in Other Hematological Malignancies 924
34.4.2 RIT in Solid Tumors 924
34.4.2.1 Colon Cancer 924
34.4.2.2 Prostate Cancer 928
34.4.2.3 Ovarian Cancer 928
34.4.2.4 Brain and Other CNS Tumors 928
34.5 Novel Radioimmunotherapy Targeting Gangliosides 929
34.6 Novel Dosimetry Method 930
34.7 Conclusions 931
References 931
35: Radioactive Microspheres 942
35.1 Introduction and Overview 942
35.2 90Y Microspheres: Commercial Preparations for Intra-arterial Therapy 943
35.3 188Re Microspheres 944
35.3.1 Example: In-House Kit Preparation of 188Re Microspheres (Fig. 35.1) 944
35.4 166Ho Microparticles 947
35.5 Microparticles for Pre-therapeutic Use 947
35.5.1 99mTc Microparticles 947
35.5.1.1 Macroaggregates 947
35.5.1.2 Microspheres 948
35.5.2 68Ga Particles 948
35.6 Particles Loading with Alpha Emitters 948
References 948
36: Radioembolization 951
36.1 Basic Principles and Indications 952
36.1.1 Radioembolization 952
36.1.2 Types of Microspheres 952
36.1.2.1 90Y Microspheres 953
TheraSphere® 953
SIR-Spheres® 953
36.1.2.2 166Ho Microspheres (QuiremSpheres®) 953
36.1.3 Patient Selection 954
36.2 Work-Up 954
36.2.1 Clinical Investigations 954
36.2.2 Laboratory Investigations 955
36.2.3 Imaging 955
36.2.3.1 Liver CT/MRI and 18FDG-PET 955
36.2.3.2 Vascular Anatomy 955
36.3 Preparatory Angiography and Intraprocedural Imaging 956
36.3.1 Intraprocedural Imaging 957
36.3.2 Coil Embolization of Culprit Vessels 958
36.4 Scout Dose Imaging and Pretreatment Dosimetry 958
36.4.1 99mTc-MAA 958
36.4.2 166Ho Scout Dose 960
36.4.3 Lung Shunt Calculation 960
36.4.4 Extrahepatic Activity and Non-tumor Dose in the Liver 961
36.4.5 Pretreatment Dosimetry 961
36.5 Treatment 963
36.5.1 Treatment Angiography 963
36.5.2 Medication 963
36.5.3 Dose Administration 964
36.5.4 Possible Side Effects and Adverse Events 964
36.5.5 Long-Term Hepatic Changes 968
36.6 Posttreatment Imaging and Dosimetry 968
36.6.1 90Y Imaging 968
36.6.1.1 90Y SPECT/CT 968
36.6.1.2 90Y PET/CT 969
36.6.1.3 90Y PET/MRI 969
36.6.2 166Ho Imaging 970
36.6.2.1 166Ho SPECT/CT 970
36.6.2.2 166Ho MRI 970
36.7 Follow-Up Imaging and Response Identification 971
36.7.1 Imaging with CT and MRI 971
36.7.2 Functional Imaging with 18FDG-PET CT and Somatostatin Receptor Analogue 972
36.7.3 Response Evaluation 972
36.7.3.1 RECIST 1.1 972
36.7.3.2 mRECIST 973
36.7.3.3 PERCIST 1.0 973
36.7.3.4 Comparison of RECIST and PERCIST Criteria 973
36.8 Response 974
36.8.1 Metastatic Colorectal Carcinoma 978
36.8.2 Neuroendocrine Neoplasms 979
36.8.3 Other Tumor Types 979
36.9 Future Directions 979
36.9.1 Retreatment 979
36.9.2 Advances in Dosimetry 980
36.9.3 Radioembolization as a Bridge to Surgery 980
36.9.4 Single-Day Sessions 981
36.9.5 Technical Advances 982
36.10 Conclusion 983
References 983
37: Assessment of Tumor Response with MRI and CT After Radioembolization 990
37.1 Introduction 990
37.2 Assessment of Tumor Morphology 990
37.2.1 RECIST/WHO 991
37.2.2 EASL Criteria 992
37.2.3 Choi Criteria 993
37.3 Assessment of Tumor Biology 993
37.3.1 DWI 994
37.3.2 Perfusion Imaging 994
37.3.3 Use of Liver-Specific MR Contrast Agents 994
37.4 Outcome for Different Tumor Entities 995
37.4.1 HCC 995
37.4.2 Metastases of Neuroendocrine Tumors (NET) 996
37.4.3 Metastases of Colorectal Carcinoma (CRC) 996
37.5 Conclusions 997
References 997
38: Radioisotope Therapy of Malignant Pleural and Peritoneal Effusions 999
38.1 Indications and Contraindications for Intracavitary Therapies with Radioisotopes 999
38.2 Application of Intracavitary Therapies with Radioisotopes 999
38.3 Side Effects of Radioisotope Therapy 1000
38.4 Radiation Protection 1000
38.5 Results of Intracavitary Therapies with Radioisotopes 1000
References 1001
39: Radiosynoviorthesis (Radiation Synovectomy) 1003
39.1 Introduction 1003
39.2 Indications 1003
39.3 Radiopharmaceuticals 1004
39.4 Mechanism of Action 1004
39.5 Local Complications After RSO 1005
39.6 Methodology 1005
39.6.1 Patient Selection 1005
39.6.2 Diagnostic Studies Prior to RSO 1006
39.6.3 Performance of RSO 1006
39.6.3.1 Joint Puncture 1006
39.6.3.2 Fluoroscopy 1007
39.6.3.3 Radiation Safety Considerations 1007
39.6.4 After RSO/Follow-Up 1007
39.7 Repetition of Radiosynoviorthesis 1010
39.8 Results 1011
References 1011
40: Radioligand Therapy in Prostate Cancer Using PSMA Ligands 1013
40.1 Introduction 1013
40.2 Indications and Procedure 1014
40.3 Response 1014
40.4 Survival 1015
40.5 Toxicity 1016
40.6 Future Perspectives 1016
References 1017