Beyond Becquerel and Biology to Precision Radiomolecular Oncology: Festschrift in Honor of Richard P. Baum

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Contents 1: Rise of the Theranostics Empire: A Commentary on Dr. Baum’s Achievements 1.1 The Beginning 1.2 The Impedance 1.3 The Fertilization 1.4 Hard Yards 1.5 Expansion of the Empire 1.6 New Capital 2: Review of F-18 FDG PET/CT in Evaluating Response to Immunotherapy Treatment 2.1 Introduction 2.2 Patterns of Response 2.2.1 Pseudoprogression 2.2.2 Hyperprogression 2.2.3 Durable Response 2.3 Mechanism 2.4 18FPET CT and irAE 2.4.1 Therapy-Related Inflammation and Inverse Relation Liver SUV/Spleen SUV [18] 2.5 Conclusion References 3: Surgery in Combination with Peptide Receptor Radionuclide Therapy: A Novel Approach for the Treatment of Advanced Neuroendocrine Tumours 3.1 Introduction 3.2 Molecular Imaging of Neuroendocrine Neoplasms 3.3 Surgical Treatment 3.4 Surgery in Combination with Peptide Receptor Radionuclide Therapy 3.5 Conclusions References 4: From Concept to Clinic and Commercialization: Cowboys Wanted 4.1 Professor Richard Baum 4.2 The Great Bexxar® Disaster 4.3 “Us Versus Them” 4.4 Intellectual Property: Who Cares? 4.5 Imaging Is Not an Easy Business 4.6 Entrepreneurs Beware 4.7 Build It and They Will Come 4.8 A Fragile Supply Chain 4.9 Future Frontiers 4.10 Concluding Remarks References 5: From Radiochemistry of the Lanthanides to 225Ac and the Interference with Richard Baum 5.1 Personal Introduction 5.2 Situation of Nuclear Medicine in the 60-th 5.3 How to Make Sort-lived Nuclides Far from Beta Stability 5.4 Optimized Extraction Chromatography 5.5 Separations Based on Szilard-Chalmers Effect 5.6 High-temperature Release Studies of Radio-lanthanides from Refractory Metals 5.7 ISOLDE and the On-line Production Lanthanide Nuclides 5.8 Isotopes in Medicine: Situation in the 60-th 5.9 Metallic Positron Emitters 5.10 The Alpha Emitters 149Tb and 225Ac 5.11 From “Radioactive Ion Beams for Bio-Medical Research” Until CERN Medicis: A New Facility 5.12 The 225Ac Story 5.13 Where the 225Ac Comes From 5.14 Summarizing References 6: “How Do You Feel About Dosimetry?” The Gretchenfrage of Radionuclide Therapy 6.1 The Gretchenfrage 6.2 The Forms of Dosimetry in a Nutshell 6.3 Dose Quantities and Dose-Response in EBRT 6.4 Dose-Response I: Radiotoxicities in Radionuclide Therapy 6.5 Dose-Response II: Tumor Response in Radionuclide Therapy 6.6 The Answer to the Gretchenfrage References 7: The LuGenIum Triptych: Ode to a Theranostic Transcriptome 7.1 Retrospective Analysis of Toxicity 7.2 Circulating NET Transcripts 7.3 Circulating NET Transcripts and SSR Imaging 7.4 Circulating NET Transcripts and PRRT 7.5 Validation Study of PRRT Genomic Signature in Blood (PPQ) for the Prediction of 177Lu-octreotate Efficacy 7.6 Validation Study of Multigene NET-Specific Circulating Transcript Signature for the Monitoring of 177Lu-octreotate Efficacy 7.7 Future Developments References 8: A Tree Can Be Recognized by Its Fruit 8.1 Introduction 8.2 Fruits of Scientist Baum 8.3 Fruits of Doctor Baum 8.3.1 Fruits of Our Friend Baum References 9: IAEA Strategy for Enhancing the Sustainability of Nuclear Medicine in Low- and Middle-Income Countries 9.1 Introduction 9.2 Key Challenges 9.3 Interventions 9.4 Results 9.4.1 Technical Cooperation Programme 9.4.2 Quality Assurance 9.4.3 Procurement 9.4.4 Education 9.4.5 Coordinated Research Activities 9.5 Conclusion References 10: Radionuclide Therapy in Brain Tumours 10.1 Introduction 10.1.1 Radionuclides Used in the Therapy 10.1.1.1 Alpha-Emitter Radionuclide 10.1.1.2 Beta-Emitter Radionuclide 10.1.2 Routes of Drug Administration 10.1.2.1 Systemic Administration of Radioconjugates 10.1.2.2 Locoregional Application of Radioconjugates 10.2 Peptide Receptor Radionuclide Therapy 10.2.1 Biologic Targets for PRRT 10.2.1.1 Neurokinin Type 1 Receptor 10.2.1.2 Glioma Chloride Channels 10.2.1.3 Somatostatin Receptor 10.2.2 Clinical Studies 10.3 Immune-Based Radionuclide Therapy 10.3.1 Biologic Targets for RIT 10.3.1.1 Tenascin-C 10.3.1.2 Epidermal Growth Factor Receptor 10.3.1.3 Neural Cell Adhesion Molecule 10.3.1.4 Histone H1 10.3.2 Future Novel Targets 10.3.2.1 Fibulin-3 10.3.3 Clinical Studies 10.3.4 Challenges and Future Directions 10.3.4.1 Challenges 10.3.4.2 The Blood-Brain Barrier (BBB) 10.3.4.3 Tumoral Heterogeneity 10.3.5 Conclusion References 11: Modern Diagnostic and Therapeutic Approaches in Thyroid Diseases: Theranostics and the Changing Role of Radioactive Isotopes 11.1 Conclusion References 12: Cardiotoxicity of Targeted Therapies: Imaging of Heart Does Matter 12.1 Cancer Targeted Therapies 12.2 Cardiotoxicity of Cancer Targeted Therapy 12.3 Diagnostic Tools to Detect Myocardial Toxicity 12.3.1 Anamnesis and Risk Stratification 12.3.2 Electrocardiography 12.3.3 Cardiac Biomarkers 12.3.4 Imaging Modalities for Cardiotoxicity Screening 12.3.4.1 Echocardiography 12.3.4.2 Cardiac Magnetic Resonance 12.3.4.3 Nuclear Positron Emission Tomography 12.3.4.4 Conventional Nuclear Imaging 12.3.4.5 Cardiac Computed Tomography, Angio-Coronary Computer Tomography 12.4 Summary References 13: The Evolution of n.c.a. 177Lu to n.c.a. 177Lu-Edotreotide for the Treatment of Neuroendocrine Tumours. Sixteen Years of Collaboration Between Zentralklinik Bad Berka and ITM 13.1 Introduction 13.2 No-Carrier-Added Lutetium-177: The Gold Standard for Radionuclide Treatment 13.3 No-Carrier-Added Lutetium-177-Edotreotide for Treatment of Neuroendocrine Tumours 13.4 Conclusion and Acknowledgements References 14: Fighting for PET in German Oncological Guidelines and for Its Reimbursement by Statutory Health Insurances References 15: Precision Oncology with PSMA-Targeted α-Particle Therapy of mCRPC 15.1 Introduction 15.2 Prostate-Specific Membrane Antigen as Biological Target 15.3 PSMA PET 15.4 PSMA β-Particle Radioligand Therapy 15.5 PSMA α-Particle Radioligand Therapy 15.5.1 Actinium-225 15.5.2 Bismuth-213 15.5.3 Thorium-227 15.5.4 Lead-212 15.5.5 Terbium-149 15.6 Summary References 16: From Radioimmunodetection to Radiomolecular Precision Oncology Via Radionanotargeting by Intelligent Multidisciplinary Radiotheragnostic Nanoparticles References 17: Nuclear Medicine and Surgery on the Way to Personalized Medicine. Ten Years of Clinical and Translational Oncology and Research References 18: PSMA Radioligand Therapy: A Revolution in the Precision Radiomolecular Oncology of Prostate Cancer References 19: The Role of Individuals for Innovation: The Nuclear Medicine Biotope References 20: Working at Isotopentherapiestation D3: A Daily Challenge or Adventure Never Stops 21: Theranostics in Australia: The Importance of Vision and Training, and the Power of Collaboration References 22: Theranostic Radiopeptides in Nuclear Oncology: Design, Preclinical Screening, and Clinical Translation 22.1 Introduction 22.2 Peptides and GPCR Targets on Tumors 22.3 Radiometals and Their Chelators in Cancer Theranostics 22.4 Metabolic Stability of Radiopeptides: The Pep-Protect Concept 22.5 Radiopeptide Agonists and Antagonists 22.6 Radiopeptide Candidates for Clinical Translation References 23: Terbium “Sisters”: More Than just a “Swiss Army Knife” 23.1 Introduction 23.2 The PET Sister: Terbium-152 23.3 The SPECT Sister: Terbium-155 23.4 The Alpha Therapy Sister: Terbium-149 23.5 The Beta TherapyPLUS Sister (β ̄/Conversion/Auger-e ̄): Terbium-161 23.6 Conclusion and Outlook References 24: High-Performance Radiopharmacy: The Base for Precision Oncology References 25: Analyzing the Science Footprint of Richard P. Baum 25.1 Introduction 25.2 Material and Methods 25.3 Results 25.4 Discussion 25.5 Conclusion References 26: Therapy of Castration-Resistant Prostate Cancer: Where Is the Place of 225Ac-PSMA? 26.1 Introduction 26.2 177Lu-PSMA Versus 225Ac-PSMA PRT in mCRPC 26.3 Efficacy of 225Ac-PSMA as a Last-Line Therapy of mCRPC 26.4 Toxicities of 225Ac-PSMA for PRLT of mCRPC 26.5 Upfront Application of 225Ac-PSMA for Therapy of mCRPC in Chemotherapy-Naïve Patients 26.6 Conclusion and Future Perspectives References 27: Sola Dosis Facit Venenum: Dosimetry for Molecular Radiotherapy in Bad Berka 27.1 Introduction 27.2 Bad Berka Dose Protocol 27.3 Dosimetry in Daily Clinical Routine 27.4 Dosimetry for PRRT 27.5 PRRT Antagonists 27.6 Dosimetry for PSMA Radioligand Therapy 27.7 Conclusions References 28: On the Use of 203Pb Imaging to Inform 212Pb Dosimetry for 203/212Pb Image-Guided Alpha-Particle Therapy for Cancer 28.1 Introduction 28.2 203Pb SPECT/CT Imaging in Advance of 212Pb α-RT 28.3 Prediction of 212Pb Dosimetry Based on 203Pb Imaging 28.4 Summary and Future Directions References 29: Radioiodine-Labeled Meta-Iodobenzylguanidine for Imaging and Treatment of Pheochromocytoma/Paraganglioma and Neuroblastoma 29.1 Introduction 29.1.1 Pheochromocytoma/Paraganglioma 29.1.1.1 Manfred Fischer 29.1.2 Neuroblastoma 29.1.2.1 Matthias Schmidt 29.2 131I-mIBG for Initial Therapy 29.3 131I-mIBG in Stage III or IV Neuroblastoma 29.4 131I-mIBG after Induction Chemotherapy 29.5 Side Effects of 131I-mIBG Therapy 29.6 Radiation Exposure/Dosimetry References 30: A (188)Rejuvenating Journey with Hercules 30.1 Aim 30.2 Materials and Methods 30.3 Results 30.4 Conclusion Reference 31: CXCR4 Theranostics: A Potential Game Changer in Solid Tumors and Hematological Malignancies 31.1 Background 31.2 CXCR4-Targeted PET Imaging in Lung Cancer 31.3 CXCR4-Targeted PET Imaging in Multiple Myeloma 31.4 CXCR4-Targeted PET Imaging in Glioblastoma Multiforme (GBM) 31.5 Conclusion References 32: Can VPAC-Targeted Cu-67-TP3805 Play a Theranostic Role for Prostate Cancer?: A Quest 32.1 Introduction 32.2 Our Approach 32.3 VPAC Receptor and Its Expression on PCa 32.4 VIP, PACAP, and Their Analogues 32.5 Synthesis of N2(S-Benzyl)2 Containing VIP and PACAP 32.6 Cu-64-TP3805 and Its Tissue Distribution in Humans 32.7 Ability of VPAC Target to Image Primary PCa, and Its Metastases in Bone and Lymph Nodes 32.8 Suitability of Cu-67 for Theranostic Application References 33: Evaluation of Real-World Efficiency of 177Lu-PSMA Radioligand Therapy of Metastatic Prostate Cancer References 34: Uptake of 68Ga-DOTATATE and 68Ga-DOTATOC in Primary Neuroendocrine Tumors, Metastases, and Normal Liver Tissue: Is There a Significant Difference? 34.1 Introduction 34.2 Methods 34.3 Results 34.4 Discussion 34.4.1 Potential Limitations 34.5 Conclusions References 35: Theranostics with Somatostatin Receptor Antagonists 35.1 Introduction 35.2 Part I. Preclinical Development of SST Antagonists for Theranostics 35.2.1 Second Generation of Radiolabelled SST Antagonists 35.3 Part II. Novel Indications for Theranostics with SST Antagonists 35.4 Part III. Clinical Development of SST Antagonists 35.4.1 Studies with Diagnostic SST Antagonists 35.4.2 Studies with Therapeutic SST Antagonists 35.5 Part IV. Current and Future Developments 35.6 Conclusion References 36: Molecular In Vitro and In Vivo Diagnostics as the Impartible Basis of Multimodal Therapy Approaches in Precision Oncology References 37: Molecular Imaging Platform and Radiopharmaceutical Translational Research on Peking University Cancer Hospital 37.1 Prof. Zhi Yang and His Team 37.2 Beijing Cancer Hospital: Nuclear Medicine Department Clinical Translation Platform 37.2.1 Introduction of the Department 37.2.2 PKUCH-NM Honored to be the First ICPO Partner 37.3 Clinical Translational Study 37.3.1 Concise Introduction 37.3.2 Clinical Evaluation of 99mTc-Rituximab for Sentinel Lymph Node Mapping 37.3.3 Tumor Amino Metabolism PET Imaging 37.4 Solid Target Radionuclide Production and Labeling Process 37.5 The Development of New Target, Novel Drug-Delivery Systems 37.5.1 Noninvasive Micro-PET Predicting Tumor Resistance to Radiotherapy 37.5.2 Synthesis of Site-Specific Radiolabeled Antibodies for RIT Via Genetic Code Expansion References 38: Is It Possible to Target HER2 Using Affibody Receptor Radionuclide Therapy? 38.1 HER2 Overexpression Tumor Model Construction 38.2 HER2 Targeting Immune-PET Imaging 38.3 HER2 Targeting Affibody PET Imaging 38.4 HER2 Targeting Therapy 38.5 HER2 Using Affibody Receptor Radionuclide Therapy 38.6 Clinical Significance of HER2 ARRT References