Intro -- Preface -- Acknowledgment -- Contents -- 1: Introduction onNuclear Medicine andImmunology -- 1.1 The Immune System: Building Blocks andMechanisms -- 1.1.1 Inflammation -- 1.1.2 Infection -- 1.1.3 Immuno-Oncology -- 1.2 Nuclear Medicine inImmune-Mediated Conditions -- 1.2.1 Infectious Diseases -- 1.2.2 Inflammatory Diseases -- 1.2.3 Radioimmunoimaging -- 1.3 Radioimmunotherapy -- 1.4 Evaluation ofTumor Response toImmunotherapy -- 1.5 Concluding Remarks -- References -- 2: Nuclear Imaging ofEndogenous Markers ofLymphocyte Response -- 2.1 Introduction -- 2.2 Strategies forImaging Endogenous Immune Biomarkers -- 2.2.1 Cell Surface Immune Markers -- 2.2.2 Intracellular Metabolic Pathways -- 2.2.3 Secreted Biomarkers -- 2.2.4 Strengths andLimitations Compared toEx Vivo Labeling Approaches -- 2.3 Imaging T Cell Responses -- 2.3.1 Overview ofT Cell Biology -- 2.3.2 T Cell Activation andProliferation -- 2.3.2.1 Targeting Cell Surface Lineage Markers -- 2.3.2.2 Targeting Cell Surface Activation Markers -- 2.3.2.3 Targeting Intracellular Metabolic Pathways -- 2.3.3 T Cell Cytotoxicity -- 2.3.4 T Cell Inhibition andControl -- 2.4 Imaging B Cell Responses -- 2.4.1 Overview ofB Cell Biology -- 2.4.1.1 Targeting Cell Surface Lineage Markers -- 2.5 Imaging Natural Killer (NK) Cell Responses -- 2.5.1 Overview ofNK Cell Biology -- 2.5.1.1 Emergence ofNK Cell Therapies -- 2.5.1.2 Candidate Endogenous Targets forNK Cell Imaging -- 2.6 Priorities andFuture Considerations -- 2.7 Conclusion -- References -- 3: Radioimaging ofActivated T Cells inPreclinical andClinical Cancer Investigations -- 3.1 Introduction -- 3.2 Direct Labeling -- 3.3 Indirect Labeling -- 3.3.1 Reporter Genes -- 3.3.1.1 Thymadine Kinase Reporter Gene Tracers -- FIAU -- FHBG -- FEAU -- 3.3.1.2 T Cell Receptor Targeting

3.3.1.3 hNIS Reporter Gene Tracer: [99mTc]TcO4− -- 3.3.1.4 hNET Reporter Gene Tracer:MIBG -- 3.3.2 Deoxyribonucleotide Salvage Pathway Reporters -- 3.3.2.1 FAC -- 3.3.2.2 CFA -- 3.3.2.3 AraG -- 3.3.2.4 FMAU -- 3.3.2.5 FLT -- 3.3.3 Interleukins -- 3.3.4 Antibodies, Antibody Fragments, andPeptides -- 3.3.4.1 PD-1 -- 3.3.4.2 Anti-CD152 (CTLA-4) mAb -- 3.3.4.3 Anti-CD3 mAb -- 3.3.4.4 Anti-CD8 mAb -- 3.3.4.5 OX40 (CD134) -- 3.3.4.6 T Cell Receptor Targeting -- 3.3.4.7 Granzyme B -- 3.4 Conclusions -- References -- 4: Gallium Imaging ofInfection andInflammation -- 4.1 Introduction -- 4.2 Infection Imaging -- 4.3 Preclinical Studies inInfection -- 4.3.1 Chlamydia -- 4.3.2 Aspergillosis -- 4.3.3 Intra-abdominal Infections -- 4.4 Clinical Studies Using Infection Imaging -- 4.4.1 Osteomyelitis -- 4.4.2 Tuberculosis -- 4.4.3 Fever ofUnknown Origin (FUO) -- 4.5 Inflammation Imaging -- 4.5.1 Nonspecific Inflammation Processes andTracers -- 4.5.2 Specific Inflammatory Processes andTracers -- 4.5.3 Tumor-Related Inflammation -- 4.6 PET Imaging ofInflammation -- 4.6.1 Central Nervous System -- 4.6.1.1 Preclinical -- 4.6.1.2 Clinical -- 4.6.2 Cardiovascular System -- 4.6.2.1 Atherosclerosis -- 4.6.2.2 Vulnerable Plaque -- 4.6.2.3 Post-myocardial Infarct Inflammation -- 4.6.2.4 Post-medical Device Implantation -- 4.6.2.5 Platelet andThrombus Imaging -- Clinical -- 4.6.3 Respiratory System -- 4.6.4 Gastrointestinal Tract (GIT) -- 4.6.5 Inflammatory Joint Diseases -- 4.7 Summary andFuture Considerations -- References -- 5: 111Indium-Labeled Leukocyte Imaging ofInfection andInflammation -- 5.1 Introduction -- 5.2 Inflammation -- 5.3 Radiolabeled Leukocytes -- 5.4 Normal Distribution andKinetics ofRadiolabeled Leukocytes -- 5.5 Pathological Distribution ofRadiolabeled Leukocytes

5.6 Clinical Applications -- 5.6.1 Clinical Guidelines -- 5.6.2 Fever ofUnknown Origin (FUO) -- 5.6.3 Infective Endocarditis andCardiac Electronic Devices -- 5.6.4 Vascular Graft Infection -- 5.6.5 Joint Prosthesis Infection -- 5.6.6 Diabetic Infections -- 5.6.7 Appendicitis -- 5.6.8 Inflammatory Bowel Disease -- 5.6.9 Rheumatoid Arthritis -- 5.7 Improvements inLeukocyte Scans -- 5.8 Conclusion -- References -- 6: [99mTc]Tc-HMPAO-Labeled Leukocyte Imaging ofInfection andInflammation -- 6.1 Introduction -- 6.2 Leukocyte Labeling Procedure -- 6.3 Biodistribution -- 6.4 Comparison of99mTc-WBC with111In-WBC Scintigraphy -- 6.5 Dosimetry -- 6.6 Infection/Inflammation Evaluation-General Considerations -- 6.7 Inflammatory Bowel Disease -- 6.8 Musculoskeletal Infections -- 6.8.1 Peripheral Bone Infections -- 6.8.2 Neuropathic Joint Versus Osteomyelitis -- 6.8.2.1 Combined WBC-Marrow Imaging -- 6.8.3 Postoperative/Prosthesis Infections -- 6.8.4 Spondylodiscitis -- 6.8.5 Chronic Infection/CMRO -- 6.8.5.1 SPECT andSPECT/CT -- 6.9 Fever ofUnknown Origin (FUO) -- 6.10 Cardiovascular Infections -- 6.10.1 Infectious Endocarditis (IE) -- 6.10.2 Mycotic Aneurysm -- 6.10.3 Vascular Graft Infection -- 6.10.4 Cardiovascular Implantable Electronic Device (CIED) Infection -- 6.11 Pulmonary Infections -- 6.11.1 Interpretation -- 6.12 Imaging pitfalls -- 6.12.1 Pitfalls inLung Imaging -- 6.12.2 Pitfalls Elsewhere intheBody -- 6.13 Other Considerations -- 6.13.1 Tumors -- 6.13.2 Eosinophilic Syndromes -- 6.13.3 Graft Versus Host Disease (GVHD) -- 6.13.4 Treatment Monitoring -- 6.14 Pediatric Population -- 6.15 Future Directions -- References -- 7: 2-[18F]FDG PET Imaging ofInfection andInflammation -- 7.1 Introduction -- 7.2 Mechanism of2-[18F]FDG Uptake inMalignant andInflammatory Cells -- 7.3 Tissue Infection

7.4 Osteomyelitis -- 7.5 Cardiac Device Infection andInflammatory Diseases oftheHeart -- 7.6 Vascular Graft Infection (Vascular Prosthesis Infection) -- 7.7 Joint Prosthesis Infection -- 7.8 Tuberculosis (TB) -- 7.9 Sarcoidosis -- 7.10 Autoimmune Diseases -- 7.10.1 Vasculitis -- 7.10.2 Inflammatory Bowel Diseases (IBD) -- 7.10.3 IgG4-Related Disease -- 7.10.4 Rheumatoid Arthritis (RA) -- 7.10.5 Other Autoimmune Diseases -- 7.11 Immune Deficiency (HIV-Related Disease) -- 7.12 Conclusion -- References -- 8: 2-[18F]FDG PET/CT inFever ofUnknown Origin -- 8.1 Introduction -- 8.2 Morphological andMolecular Imaging -- 8.3 2-[18F]FDG PET/CT inFUO -- 8.4 Timing of2-[18F]FDG PET/CT inFUO -- 8.5 Cost-Effectiveness -- 8.6 Conclusion -- References -- 9: Tumor-Targeting Agents -- 9.1 Introduction -- 9.2 Ligand Targeted Therapy -- 9.3 Antibody -- 9.3.1 Monoclonal Antibody -- 9.3.1.1 Immune Response toMonoclonal Antibodies -- 9.3.1.2 Antibody Engineering -- 9.3.2 Antibody Fragments Variations -- 9.3.2.1 Characteristics ofAntibody Fragments -- Conjugated Antibody -- 9.3.3 Pretargeting -- 9.4 Small Molecule Inhibitors Targeting Kinases -- 9.4.1 Structure andMode ofAction ofSmall Molecule Inhibitors -- 9.4.2 Limitations ofSmall Molecule Inhibitors asTargeted Cancer Therapy -- 9.5 Development ofNewer Drugs -- 9.5.1 Selective High-Affinity Ligand (SHAL) -- 9.5.2 Phage Display Technique forNew Targeting Ligands -- 9.6 Selective Small Molecule Targeted Radionuclide Imaging/Therapy -- 9.6.1 Tumor Receptor Targeting withRadiolabeled Peptides -- 9.6.2 Radioligand Targeted Diagnosis andTherapeutics inProstate Cancer -- 9.6.2.1 Monoclonal Antibodies -- 9.6.2.2 Small Molecule Inhibitors -- 9.7 The Use ofNano-Drug Carrier -- 9.8 Aptamers -- 9.9 Conclusion -- References -- 10: Tumor Architecture andTargeted Delivery

10.1 Introduction -- 10.2 Organization oftheSolid Tumor -- 10.2.1 Parenchymal Component -- 10.2.2 Stromal Component -- 10.2.3 Cancer-Associated Fibroblasts (CAF) -- 10.3 Cancer Metastasis -- 10.4 Angiogenesis -- 10.5 Tumor Vascular Architecture -- 10.6 Transport Across theMicrovascular Wall -- 10.7 Transport Across theStroma -- 10.8 Transport Across theParenchyma -- 10.9 Strategies toReduce theBarriers fortheMacromolecules toReach Their Target -- 10.10 Drug Delivery inCancer -- 10.10.1 Drug Delivery Targeting Tumor Vasculature -- 10.10.1.1 Passive Targeting -- 10.10.1.2 Active Targeting -- 10.10.2 Increase inBlood Circulation Time andReduced Immunogenicity -- 10.10.3 Drug Release Based ontheTumor Microenvironment -- 10.10.4 Prodrug Mechanism -- 10.10.5 Drug Delivery by Modulation ofTumor Vasculature -- 10.11 Conclusion -- References -- 11: Radionuclide Therapy andImmunomodulation -- 11.1 Introduction -- 11.2 The Role oftheImmune System inRadiotherapy -- 11.2.1 External Beam Radiation Therapy andAbscopal Responses -- 11.2.2 Immunomodulation by EBRT Can Contribute toTherapeutic Efficacy -- 11.2.3 Molecular Understanding ofImmunomodulation byEBRT -- 11.2.3.1 Increasing Sensitivity ofTumor Cells toCytotoxic Immune Cells -- 11.2.3.2 Lymphocyte Activation -- 11.2.3.3 Lymphocyte Recruitment -- 11.2.3.4 Innate Immune Activation -- 11.2.3.5 Concurrent Immuno suppressive Effects -- 11.3 Targeted Radionuclide Therapy andtheImmune System -- 11.3.1 Understanding theMechanisms ofImmune Activation by TRT (Preclinical Evidence) -- 11.3.2 Clinical Evidence foranImmune Response -- 11.4 Conclusion -- References -- 12: Translational Development andTesting ofTheranostics inCombination withImmunotherapies -- 12.1 Introduction -- 12.2 Rationale forCombining Radiation andImmunotherapy

12.2.1 Immunomodulatory Effects ofRadiation onTumor Cells