Monoclonal Antibody and Peptide-Targeted Radiotherapy of Cancer
Herausgegeben von Reilly, Raymond M.
Monoclonal Antibody and Peptide-Targeted Radiotherapy of Cancer
Herausgegeben von Reilly, Raymond M.
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Oncology Book of 2011, British Medical Association s Medical Book Awards Awarded first prize in the Oncology category at the 2011 BMA Medical Book Awards, Monoclonal Antibody and Peptide-Targeted Radiotherapy of Cancer helps readers understand this hot pharmaceutical field with up-to-date developments. Expert discussion covers a range of diverse topics associated with this field, including the optimization of design of biomolecules and radiochemistry, cell and animal models for preclinical evaluation, discoveries from key clinical trials, radiation biology and dosimetry, and considerations in…mehr
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Oncology Book of 2011, British Medical Association s Medical Book Awards
Awarded first prize in the Oncology category at the 2011 BMA Medical Book Awards, Monoclonal Antibody and Peptide-Targeted Radiotherapy of Cancer helps readers understand this hot pharmaceutical field with up-to-date developments. Expert discussion covers a range of diverse topics associated with this field, including the optimization of design of biomolecules and radiochemistry, cell and animal models for preclinical evaluation, discoveries from key clinical trials, radiation biology and dosimetry, and considerations in regulatory approval. With chapters authored by internationally renowned experts, this book delivers a wealth of information to push future discovery.
Awarded first prize in the Oncology category at the 2011 BMA Medical Book Awards, Monoclonal Antibody and Peptide-Targeted Radiotherapy of Cancer helps readers understand this hot pharmaceutical field with up-to-date developments. Expert discussion covers a range of diverse topics associated with this field, including the optimization of design of biomolecules and radiochemistry, cell and animal models for preclinical evaluation, discoveries from key clinical trials, radiation biology and dosimetry, and considerations in regulatory approval. With chapters authored by internationally renowned experts, this book delivers a wealth of information to push future discovery.
Produktdetails
- Produktdetails
- Verlag: Wiley & Sons
- Artikelnr. des Verlages: 14524372000
- 1. Auflage
- Seitenzahl: 648
- Erscheinungstermin: 2. August 2010
- Englisch
- Abmessung: 246mm x 167mm x 40mm
- Gewicht: 1103g
- ISBN-13: 9780470243725
- ISBN-10: 0470243724
- Artikelnr.: 29929508
- Verlag: Wiley & Sons
- Artikelnr. des Verlages: 14524372000
- 1. Auflage
- Seitenzahl: 648
- Erscheinungstermin: 2. August 2010
- Englisch
- Abmessung: 246mm x 167mm x 40mm
- Gewicht: 1103g
- ISBN-13: 9780470243725
- ISBN-10: 0470243724
- Artikelnr.: 29929508
RAYMOND M. REILLY is a Professor in the Leslie Dan Faculty of Pharmacy at the University of Toronto. He has more than twenty years of experience in the field of radiolabeled antibody and peptide targeting of cancer. Dr. Reilly has written over 180 publications in the field, including more than 100 scientific papers on radiopharmaceuticals for cancer imaging and targeted radiotherapy.
Preface. Contributors. 1. Antibody Engineering: Optimizing the Delivery
Vehicle (Diane E. Milenic). 1.1 Introduction. 1.2 Intact Murine Monoclonal
Antibodies. 1.3 Recombinant Immunoglobulin Molecules. 1.4 Nanobodies. 1.5
Domain-Deleted Monoclonal Antibodies. 1.6 Hypervariable Domain Region
Peptides. 1.7 Fv Fragments. 1.8 Minibodies. 1.9 Selective High Affinity
Ligands. 1.10 Affibodies. 1.11 Other Strategies. 1.12 Concluding Remarks.
References. 2. The Radiochemistry of Monoclonal Antibodies and Peptides
(Raymond M. Reilly). 2.1 Introduction. 2.2 Tumor and Normal Tissue Uptake
of Monoclonal Antibodies and Peptides. 2.3 Selection of a Radionuclide for
Tumor Imaging. 2.4 Selection of a Radionuclide for Targeted Radiotherapy.
2.5 Labeling Antibodies and Peptides with Radiohalogens. 2.6 Labeling
Antibodies and Peptides with Radiometals. 2.7 Characterization of
Radiolabeled mAbs and Peptides. 2.8 Summary. Acknowledgments. References.
3. The Design of Radiolabeled Peptides for Targeting Malignancies (Leonard
G. Luyt). 3.1 Introduction. 3.2 Peptide Targets. 3.3 Peptides as Cancer
Targeting Agents. 3.4 Multimodality Agents. 3.5 Future Outlook. References.
4. Peptide Receptor Radionuclide Therapy in Patients with Somatostatin
Receptor-Positive Neuroendocrine Tumors (Martijn van Essen, Dik J.
Kwekkeboom, Wouter W. de Herder, Lisa Bodei, Boen L. R. Kam, Marion de
Jong, Roelf Valkema, and Eric P. Krenning). 4.1 Introduction. 4.2
Radiotherapy with 111In-Octreotide. 4.3 Radiotherapy with 90Y-DOTATOC. 4.4
Targeted Radiotherapy Studies with 177Lu-Octreotate. 4.5 PRRT with Other
Somatostatin Analogues. 4.6 Comparison of Different PRRT Studies. 4.7
Comparison with Chemotherapy. 4.8 Options for Improving PRRT and Future
Directions. 4.9 Conclusions. References. 5. Targeted Radiotherapy of
Central Nervous System Malignancies (Michael R. Zalutsky, David A. Reardon,
and Darell D. Bigner). 5.1 Malignant Brain Tumors. 5.2 Rationale for
Locoregional Therapy. 5.3 Targeted Radiotherapy of Brain Tumors. 5.4
Rationale for Tenascin-C as a Target for Radionuclide Therapy. 5.5
Perspective for the Future. Acknowledgments. References. 6.
Radioimmunotherapy for B-Cell Non-Hodgkin Lymphoma (Thomas E. Witzig). 6.1
Introduction. 6.2 Radioimmunotherapy. 6.3 Antibodies Against CD22. 6.4 RIT
Versus Immunotherapy. 6.5 RIT in Rituximab Refractory Patients. 6.6 RIT for
Previously Untreated Patients. 6.7 RIT for Relapsed Large-Cell Lymphoma.
6.8 RIT for Transformed Lymphoma. 6.9 RIT for Mantle Cell Lymphoma. 6.10
Long-Term Results of RIT. 6.11 Risk of Myelodysplasia with RIT. 6.12
Feasibility of Treatment After RIT Failure. 6.13 Combinations of RIT and
Chemotherapy. 6.14 High-Dose RIT with Stem Cell Support. 6.15 RIT for
Central Nervous System Lymphoma. 6.16 Retreatment with RIT. 6.17 RIT in
Children with Relapsed NHL. 6.18 RIT in Patients with Lung Involvement.
6.19 RIT in Patients with Skin Lymphoma. 6.20 RIT in Patients with >25%
Marrow Involvement. 6.21 RIT in Older Patients. 6.22 RIT in Hodgkin's
Disease. 6.23 Viral Infections After RIT. 6.24 Radiation Therapy After RIT.
6.25 Summary. 6.26 Future Directions. References. 7. Radioimmunotherapy of
Acute Myeloid Leukemia (Todd L. Rosenblat and Joseph G. Jurcic). 7.1
Introduction. 7.2 Antigenic Targets. 7.3 Radionuclide Selection. 7.4
Radiolabeling. 7.5 Pharmacokinetics and Dosimetry. 7.6 RIT with b-Particle
Emitters. 7.7 RIT with a-Particle Emitters. 7.8 Summary. References. 8.
Pretargeted Radioimmunotherapy of Cancer (Robert M. Sharkey and David G.
Goldenberg). 8.1 Introduction. 8.2 The Challenge of Improving
Tumor/Nontumor Ratios. 8.3 Pretargeting: Uncoupling the
Antibody-Radionuclide Conjugate. 8.4 Clinical Studies of Pretargeting. 8.5
Prospects for Combination Therapies. 8.6 Future Innovations. 8.7
Conclusions. References. 9. Targeted Auger Electron Radiotherapy of
Malignancies (Raymond M. Reilly and Amin Kassis). 9.1 Introduction. 9.2
Radiobiological Effects of Auger Electrons. 9.3 Selection of an Auger
Electron-Emitting Radionuclide. 9.4 Microdosimetry. 9.5 Molecular Targets
for Auger Electron Radiotherapy of Cancer. 9.6 Small-Molecule Auger
Electron Radiotherapy. 9.7 Summary and Conclusions. Acknowledgments.
References. 10. Viral Introduction of Receptors for Targeted Radiotherapy
(Kathryn Ottolino-Perry and Judith Andrea McCart). 10.1 Introduction. 10.2
Viral Vectors. 10.3 Virally Delivered Receptors. 10.4 Combined Oncolytic
and Targeted Radiotherapy. 10.5 Summary. References. 11. Preclinical Cell
and Tumor Models for Evaluating Radiopharmaceuticals in Oncology (Ann F.
Chambers, Eva A. Turley, John Lewis, and Leonard G. Luyt). 11.1
Introduction. 11.2 Traditional Approaches to Preclinical Evaluation of
Radiotherapeutics. 11.3 Models of Cancer. 11.4 Animal Models for Evaluating
Radiopharmaceuticals: Unresolved Issues and Challenges for Translation.
References. 12. Radiation Biology of Targeted Radiotherapy (David Murray
and Michael Weinfeld). 12.1 Introduction. 12.2 Targeted Radionuclide
Therapy: Concepts. 12.3 Radiation-Induced DNA Damage. 12.4 Cellular DNA
Damage Surveillance-Response Networks. 12.5 Mammalian DNA-Repair Pathways.
12.6 Modes of Cell Death Following Radiation Exposure. 12.7 Conventional
Models for Cell Survival Curves, Fractionation, and Dose-Rate Effects. 12.8
Low-Dose Hyperradiosensitivity-Increased Radioresistance. 12.9 Inverse
Dose-Rate Effects. 12.10 Cross fire. 12.11 The Radiobiological Bystander
Effect. 12.12 The Adaptive Response. 12.13 A Possible Contribution from
Low-Dose Radiobiological Mechanisms to TRT Tumor. Responses?. 12.14 Use of
Radionuclides Other Than b-Particle Emitters. 12.15 Role of Tumor Hypoxia
and Fractionation Effects. 12.16 Summary and Future Directions.
Acknowledgments. References. 13. Dosimetry for Targeted Radiotherapy (Sui
Shen and John B. Fiveash). 13.1 Introduction. 13.2 Basic Concepts of MIRD
Dosimetry. 13.3 Preclinical Dosimetry. 13.4 Clinical Dosimetry Methods.
13.5 Dosimetry for Dose-Limiting Organs and Tumors. 13.6 Conclusions.
References. 14. The Bystander Effect in Targeted Radiotherapy (Carmel
Mothersill and Colin Seymour). 14.1 Introduction. 14.2 Historical Review of
Bystander Effects in the Context of Radiation Damage to Cells. 14.3 New
Knowledge and the Pillars of the Developing New Paradigm. 14.4 Concept of
Hierarchical Levels of Assessment of Targeted Radiation Effects. 14.5 The
New Meaning of the LNT Model. 14.6 Techniques for Studying Bystander
Effects. 14.7 Bystander Phenomena in Targeted and Conventional
Radiotherapy. 14.8. Mechanisms Underlying Bystander Effects and Detection
Techniques. 14.9. The Future. References. 15. The Role of Molecular Imaging
in Evaluating Tumor Response to Targeted Radiotherapy (Norbert Avril). 15.1
Introduction. 15.2 Positron Emission Tomography. 15.3 Response to Cancer
Treatment Including Targeted Radiotherapy. References. 16. The Economic
Attractiveness of Targeted Radiotherapy: Value for Money? (Jeffrey S.
Hoch). 16.1 Introduction. 16.2 Applying Economics in Theory. 16.3 Applying
Economics in Practice. 16.4 The Economic Attractiveness of Targeted
Radiotherapy: the Case of 90Y-Ibritumomab Tiuxetan (Zevalin). 16.5
Conclusions. References. 17. Selected Regulatory Elements in the
Development of Protein and Peptide Targeted Radiotherapeutic Agents (Thomas
R. Sykes and Connie J. Sykes). 17.1 Introduction. 17.2 Administrative and
Organizational Elements. 17.3 Pharmaceutical Quality Elements. 17.4
Nonclinical Study Elements. 17.5 Clinical Study Elements. 17.6 Summary.
Dedication. References. Index.
Vehicle (Diane E. Milenic). 1.1 Introduction. 1.2 Intact Murine Monoclonal
Antibodies. 1.3 Recombinant Immunoglobulin Molecules. 1.4 Nanobodies. 1.5
Domain-Deleted Monoclonal Antibodies. 1.6 Hypervariable Domain Region
Peptides. 1.7 Fv Fragments. 1.8 Minibodies. 1.9 Selective High Affinity
Ligands. 1.10 Affibodies. 1.11 Other Strategies. 1.12 Concluding Remarks.
References. 2. The Radiochemistry of Monoclonal Antibodies and Peptides
(Raymond M. Reilly). 2.1 Introduction. 2.2 Tumor and Normal Tissue Uptake
of Monoclonal Antibodies and Peptides. 2.3 Selection of a Radionuclide for
Tumor Imaging. 2.4 Selection of a Radionuclide for Targeted Radiotherapy.
2.5 Labeling Antibodies and Peptides with Radiohalogens. 2.6 Labeling
Antibodies and Peptides with Radiometals. 2.7 Characterization of
Radiolabeled mAbs and Peptides. 2.8 Summary. Acknowledgments. References.
3. The Design of Radiolabeled Peptides for Targeting Malignancies (Leonard
G. Luyt). 3.1 Introduction. 3.2 Peptide Targets. 3.3 Peptides as Cancer
Targeting Agents. 3.4 Multimodality Agents. 3.5 Future Outlook. References.
4. Peptide Receptor Radionuclide Therapy in Patients with Somatostatin
Receptor-Positive Neuroendocrine Tumors (Martijn van Essen, Dik J.
Kwekkeboom, Wouter W. de Herder, Lisa Bodei, Boen L. R. Kam, Marion de
Jong, Roelf Valkema, and Eric P. Krenning). 4.1 Introduction. 4.2
Radiotherapy with 111In-Octreotide. 4.3 Radiotherapy with 90Y-DOTATOC. 4.4
Targeted Radiotherapy Studies with 177Lu-Octreotate. 4.5 PRRT with Other
Somatostatin Analogues. 4.6 Comparison of Different PRRT Studies. 4.7
Comparison with Chemotherapy. 4.8 Options for Improving PRRT and Future
Directions. 4.9 Conclusions. References. 5. Targeted Radiotherapy of
Central Nervous System Malignancies (Michael R. Zalutsky, David A. Reardon,
and Darell D. Bigner). 5.1 Malignant Brain Tumors. 5.2 Rationale for
Locoregional Therapy. 5.3 Targeted Radiotherapy of Brain Tumors. 5.4
Rationale for Tenascin-C as a Target for Radionuclide Therapy. 5.5
Perspective for the Future. Acknowledgments. References. 6.
Radioimmunotherapy for B-Cell Non-Hodgkin Lymphoma (Thomas E. Witzig). 6.1
Introduction. 6.2 Radioimmunotherapy. 6.3 Antibodies Against CD22. 6.4 RIT
Versus Immunotherapy. 6.5 RIT in Rituximab Refractory Patients. 6.6 RIT for
Previously Untreated Patients. 6.7 RIT for Relapsed Large-Cell Lymphoma.
6.8 RIT for Transformed Lymphoma. 6.9 RIT for Mantle Cell Lymphoma. 6.10
Long-Term Results of RIT. 6.11 Risk of Myelodysplasia with RIT. 6.12
Feasibility of Treatment After RIT Failure. 6.13 Combinations of RIT and
Chemotherapy. 6.14 High-Dose RIT with Stem Cell Support. 6.15 RIT for
Central Nervous System Lymphoma. 6.16 Retreatment with RIT. 6.17 RIT in
Children with Relapsed NHL. 6.18 RIT in Patients with Lung Involvement.
6.19 RIT in Patients with Skin Lymphoma. 6.20 RIT in Patients with >25%
Marrow Involvement. 6.21 RIT in Older Patients. 6.22 RIT in Hodgkin's
Disease. 6.23 Viral Infections After RIT. 6.24 Radiation Therapy After RIT.
6.25 Summary. 6.26 Future Directions. References. 7. Radioimmunotherapy of
Acute Myeloid Leukemia (Todd L. Rosenblat and Joseph G. Jurcic). 7.1
Introduction. 7.2 Antigenic Targets. 7.3 Radionuclide Selection. 7.4
Radiolabeling. 7.5 Pharmacokinetics and Dosimetry. 7.6 RIT with b-Particle
Emitters. 7.7 RIT with a-Particle Emitters. 7.8 Summary. References. 8.
Pretargeted Radioimmunotherapy of Cancer (Robert M. Sharkey and David G.
Goldenberg). 8.1 Introduction. 8.2 The Challenge of Improving
Tumor/Nontumor Ratios. 8.3 Pretargeting: Uncoupling the
Antibody-Radionuclide Conjugate. 8.4 Clinical Studies of Pretargeting. 8.5
Prospects for Combination Therapies. 8.6 Future Innovations. 8.7
Conclusions. References. 9. Targeted Auger Electron Radiotherapy of
Malignancies (Raymond M. Reilly and Amin Kassis). 9.1 Introduction. 9.2
Radiobiological Effects of Auger Electrons. 9.3 Selection of an Auger
Electron-Emitting Radionuclide. 9.4 Microdosimetry. 9.5 Molecular Targets
for Auger Electron Radiotherapy of Cancer. 9.6 Small-Molecule Auger
Electron Radiotherapy. 9.7 Summary and Conclusions. Acknowledgments.
References. 10. Viral Introduction of Receptors for Targeted Radiotherapy
(Kathryn Ottolino-Perry and Judith Andrea McCart). 10.1 Introduction. 10.2
Viral Vectors. 10.3 Virally Delivered Receptors. 10.4 Combined Oncolytic
and Targeted Radiotherapy. 10.5 Summary. References. 11. Preclinical Cell
and Tumor Models for Evaluating Radiopharmaceuticals in Oncology (Ann F.
Chambers, Eva A. Turley, John Lewis, and Leonard G. Luyt). 11.1
Introduction. 11.2 Traditional Approaches to Preclinical Evaluation of
Radiotherapeutics. 11.3 Models of Cancer. 11.4 Animal Models for Evaluating
Radiopharmaceuticals: Unresolved Issues and Challenges for Translation.
References. 12. Radiation Biology of Targeted Radiotherapy (David Murray
and Michael Weinfeld). 12.1 Introduction. 12.2 Targeted Radionuclide
Therapy: Concepts. 12.3 Radiation-Induced DNA Damage. 12.4 Cellular DNA
Damage Surveillance-Response Networks. 12.5 Mammalian DNA-Repair Pathways.
12.6 Modes of Cell Death Following Radiation Exposure. 12.7 Conventional
Models for Cell Survival Curves, Fractionation, and Dose-Rate Effects. 12.8
Low-Dose Hyperradiosensitivity-Increased Radioresistance. 12.9 Inverse
Dose-Rate Effects. 12.10 Cross fire. 12.11 The Radiobiological Bystander
Effect. 12.12 The Adaptive Response. 12.13 A Possible Contribution from
Low-Dose Radiobiological Mechanisms to TRT Tumor. Responses?. 12.14 Use of
Radionuclides Other Than b-Particle Emitters. 12.15 Role of Tumor Hypoxia
and Fractionation Effects. 12.16 Summary and Future Directions.
Acknowledgments. References. 13. Dosimetry for Targeted Radiotherapy (Sui
Shen and John B. Fiveash). 13.1 Introduction. 13.2 Basic Concepts of MIRD
Dosimetry. 13.3 Preclinical Dosimetry. 13.4 Clinical Dosimetry Methods.
13.5 Dosimetry for Dose-Limiting Organs and Tumors. 13.6 Conclusions.
References. 14. The Bystander Effect in Targeted Radiotherapy (Carmel
Mothersill and Colin Seymour). 14.1 Introduction. 14.2 Historical Review of
Bystander Effects in the Context of Radiation Damage to Cells. 14.3 New
Knowledge and the Pillars of the Developing New Paradigm. 14.4 Concept of
Hierarchical Levels of Assessment of Targeted Radiation Effects. 14.5 The
New Meaning of the LNT Model. 14.6 Techniques for Studying Bystander
Effects. 14.7 Bystander Phenomena in Targeted and Conventional
Radiotherapy. 14.8. Mechanisms Underlying Bystander Effects and Detection
Techniques. 14.9. The Future. References. 15. The Role of Molecular Imaging
in Evaluating Tumor Response to Targeted Radiotherapy (Norbert Avril). 15.1
Introduction. 15.2 Positron Emission Tomography. 15.3 Response to Cancer
Treatment Including Targeted Radiotherapy. References. 16. The Economic
Attractiveness of Targeted Radiotherapy: Value for Money? (Jeffrey S.
Hoch). 16.1 Introduction. 16.2 Applying Economics in Theory. 16.3 Applying
Economics in Practice. 16.4 The Economic Attractiveness of Targeted
Radiotherapy: the Case of 90Y-Ibritumomab Tiuxetan (Zevalin). 16.5
Conclusions. References. 17. Selected Regulatory Elements in the
Development of Protein and Peptide Targeted Radiotherapeutic Agents (Thomas
R. Sykes and Connie J. Sykes). 17.1 Introduction. 17.2 Administrative and
Organizational Elements. 17.3 Pharmaceutical Quality Elements. 17.4
Nonclinical Study Elements. 17.5 Clinical Study Elements. 17.6 Summary.
Dedication. References. Index.
Preface. Contributors. 1. Antibody Engineering: Optimizing the Delivery
Vehicle (Diane E. Milenic). 1.1 Introduction. 1.2 Intact Murine Monoclonal
Antibodies. 1.3 Recombinant Immunoglobulin Molecules. 1.4 Nanobodies. 1.5
Domain-Deleted Monoclonal Antibodies. 1.6 Hypervariable Domain Region
Peptides. 1.7 Fv Fragments. 1.8 Minibodies. 1.9 Selective High Affinity
Ligands. 1.10 Affibodies. 1.11 Other Strategies. 1.12 Concluding Remarks.
References. 2. The Radiochemistry of Monoclonal Antibodies and Peptides
(Raymond M. Reilly). 2.1 Introduction. 2.2 Tumor and Normal Tissue Uptake
of Monoclonal Antibodies and Peptides. 2.3 Selection of a Radionuclide for
Tumor Imaging. 2.4 Selection of a Radionuclide for Targeted Radiotherapy.
2.5 Labeling Antibodies and Peptides with Radiohalogens. 2.6 Labeling
Antibodies and Peptides with Radiometals. 2.7 Characterization of
Radiolabeled mAbs and Peptides. 2.8 Summary. Acknowledgments. References.
3. The Design of Radiolabeled Peptides for Targeting Malignancies (Leonard
G. Luyt). 3.1 Introduction. 3.2 Peptide Targets. 3.3 Peptides as Cancer
Targeting Agents. 3.4 Multimodality Agents. 3.5 Future Outlook. References.
4. Peptide Receptor Radionuclide Therapy in Patients with Somatostatin
Receptor-Positive Neuroendocrine Tumors (Martijn van Essen, Dik J.
Kwekkeboom, Wouter W. de Herder, Lisa Bodei, Boen L. R. Kam, Marion de
Jong, Roelf Valkema, and Eric P. Krenning). 4.1 Introduction. 4.2
Radiotherapy with 111In-Octreotide. 4.3 Radiotherapy with 90Y-DOTATOC. 4.4
Targeted Radiotherapy Studies with 177Lu-Octreotate. 4.5 PRRT with Other
Somatostatin Analogues. 4.6 Comparison of Different PRRT Studies. 4.7
Comparison with Chemotherapy. 4.8 Options for Improving PRRT and Future
Directions. 4.9 Conclusions. References. 5. Targeted Radiotherapy of
Central Nervous System Malignancies (Michael R. Zalutsky, David A. Reardon,
and Darell D. Bigner). 5.1 Malignant Brain Tumors. 5.2 Rationale for
Locoregional Therapy. 5.3 Targeted Radiotherapy of Brain Tumors. 5.4
Rationale for Tenascin-C as a Target for Radionuclide Therapy. 5.5
Perspective for the Future. Acknowledgments. References. 6.
Radioimmunotherapy for B-Cell Non-Hodgkin Lymphoma (Thomas E. Witzig). 6.1
Introduction. 6.2 Radioimmunotherapy. 6.3 Antibodies Against CD22. 6.4 RIT
Versus Immunotherapy. 6.5 RIT in Rituximab Refractory Patients. 6.6 RIT for
Previously Untreated Patients. 6.7 RIT for Relapsed Large-Cell Lymphoma.
6.8 RIT for Transformed Lymphoma. 6.9 RIT for Mantle Cell Lymphoma. 6.10
Long-Term Results of RIT. 6.11 Risk of Myelodysplasia with RIT. 6.12
Feasibility of Treatment After RIT Failure. 6.13 Combinations of RIT and
Chemotherapy. 6.14 High-Dose RIT with Stem Cell Support. 6.15 RIT for
Central Nervous System Lymphoma. 6.16 Retreatment with RIT. 6.17 RIT in
Children with Relapsed NHL. 6.18 RIT in Patients with Lung Involvement.
6.19 RIT in Patients with Skin Lymphoma. 6.20 RIT in Patients with >25%
Marrow Involvement. 6.21 RIT in Older Patients. 6.22 RIT in Hodgkin's
Disease. 6.23 Viral Infections After RIT. 6.24 Radiation Therapy After RIT.
6.25 Summary. 6.26 Future Directions. References. 7. Radioimmunotherapy of
Acute Myeloid Leukemia (Todd L. Rosenblat and Joseph G. Jurcic). 7.1
Introduction. 7.2 Antigenic Targets. 7.3 Radionuclide Selection. 7.4
Radiolabeling. 7.5 Pharmacokinetics and Dosimetry. 7.6 RIT with b-Particle
Emitters. 7.7 RIT with a-Particle Emitters. 7.8 Summary. References. 8.
Pretargeted Radioimmunotherapy of Cancer (Robert M. Sharkey and David G.
Goldenberg). 8.1 Introduction. 8.2 The Challenge of Improving
Tumor/Nontumor Ratios. 8.3 Pretargeting: Uncoupling the
Antibody-Radionuclide Conjugate. 8.4 Clinical Studies of Pretargeting. 8.5
Prospects for Combination Therapies. 8.6 Future Innovations. 8.7
Conclusions. References. 9. Targeted Auger Electron Radiotherapy of
Malignancies (Raymond M. Reilly and Amin Kassis). 9.1 Introduction. 9.2
Radiobiological Effects of Auger Electrons. 9.3 Selection of an Auger
Electron-Emitting Radionuclide. 9.4 Microdosimetry. 9.5 Molecular Targets
for Auger Electron Radiotherapy of Cancer. 9.6 Small-Molecule Auger
Electron Radiotherapy. 9.7 Summary and Conclusions. Acknowledgments.
References. 10. Viral Introduction of Receptors for Targeted Radiotherapy
(Kathryn Ottolino-Perry and Judith Andrea McCart). 10.1 Introduction. 10.2
Viral Vectors. 10.3 Virally Delivered Receptors. 10.4 Combined Oncolytic
and Targeted Radiotherapy. 10.5 Summary. References. 11. Preclinical Cell
and Tumor Models for Evaluating Radiopharmaceuticals in Oncology (Ann F.
Chambers, Eva A. Turley, John Lewis, and Leonard G. Luyt). 11.1
Introduction. 11.2 Traditional Approaches to Preclinical Evaluation of
Radiotherapeutics. 11.3 Models of Cancer. 11.4 Animal Models for Evaluating
Radiopharmaceuticals: Unresolved Issues and Challenges for Translation.
References. 12. Radiation Biology of Targeted Radiotherapy (David Murray
and Michael Weinfeld). 12.1 Introduction. 12.2 Targeted Radionuclide
Therapy: Concepts. 12.3 Radiation-Induced DNA Damage. 12.4 Cellular DNA
Damage Surveillance-Response Networks. 12.5 Mammalian DNA-Repair Pathways.
12.6 Modes of Cell Death Following Radiation Exposure. 12.7 Conventional
Models for Cell Survival Curves, Fractionation, and Dose-Rate Effects. 12.8
Low-Dose Hyperradiosensitivity-Increased Radioresistance. 12.9 Inverse
Dose-Rate Effects. 12.10 Cross fire. 12.11 The Radiobiological Bystander
Effect. 12.12 The Adaptive Response. 12.13 A Possible Contribution from
Low-Dose Radiobiological Mechanisms to TRT Tumor. Responses?. 12.14 Use of
Radionuclides Other Than b-Particle Emitters. 12.15 Role of Tumor Hypoxia
and Fractionation Effects. 12.16 Summary and Future Directions.
Acknowledgments. References. 13. Dosimetry for Targeted Radiotherapy (Sui
Shen and John B. Fiveash). 13.1 Introduction. 13.2 Basic Concepts of MIRD
Dosimetry. 13.3 Preclinical Dosimetry. 13.4 Clinical Dosimetry Methods.
13.5 Dosimetry for Dose-Limiting Organs and Tumors. 13.6 Conclusions.
References. 14. The Bystander Effect in Targeted Radiotherapy (Carmel
Mothersill and Colin Seymour). 14.1 Introduction. 14.2 Historical Review of
Bystander Effects in the Context of Radiation Damage to Cells. 14.3 New
Knowledge and the Pillars of the Developing New Paradigm. 14.4 Concept of
Hierarchical Levels of Assessment of Targeted Radiation Effects. 14.5 The
New Meaning of the LNT Model. 14.6 Techniques for Studying Bystander
Effects. 14.7 Bystander Phenomena in Targeted and Conventional
Radiotherapy. 14.8. Mechanisms Underlying Bystander Effects and Detection
Techniques. 14.9. The Future. References. 15. The Role of Molecular Imaging
in Evaluating Tumor Response to Targeted Radiotherapy (Norbert Avril). 15.1
Introduction. 15.2 Positron Emission Tomography. 15.3 Response to Cancer
Treatment Including Targeted Radiotherapy. References. 16. The Economic
Attractiveness of Targeted Radiotherapy: Value for Money? (Jeffrey S.
Hoch). 16.1 Introduction. 16.2 Applying Economics in Theory. 16.3 Applying
Economics in Practice. 16.4 The Economic Attractiveness of Targeted
Radiotherapy: the Case of 90Y-Ibritumomab Tiuxetan (Zevalin). 16.5
Conclusions. References. 17. Selected Regulatory Elements in the
Development of Protein and Peptide Targeted Radiotherapeutic Agents (Thomas
R. Sykes and Connie J. Sykes). 17.1 Introduction. 17.2 Administrative and
Organizational Elements. 17.3 Pharmaceutical Quality Elements. 17.4
Nonclinical Study Elements. 17.5 Clinical Study Elements. 17.6 Summary.
Dedication. References. Index.
Vehicle (Diane E. Milenic). 1.1 Introduction. 1.2 Intact Murine Monoclonal
Antibodies. 1.3 Recombinant Immunoglobulin Molecules. 1.4 Nanobodies. 1.5
Domain-Deleted Monoclonal Antibodies. 1.6 Hypervariable Domain Region
Peptides. 1.7 Fv Fragments. 1.8 Minibodies. 1.9 Selective High Affinity
Ligands. 1.10 Affibodies. 1.11 Other Strategies. 1.12 Concluding Remarks.
References. 2. The Radiochemistry of Monoclonal Antibodies and Peptides
(Raymond M. Reilly). 2.1 Introduction. 2.2 Tumor and Normal Tissue Uptake
of Monoclonal Antibodies and Peptides. 2.3 Selection of a Radionuclide for
Tumor Imaging. 2.4 Selection of a Radionuclide for Targeted Radiotherapy.
2.5 Labeling Antibodies and Peptides with Radiohalogens. 2.6 Labeling
Antibodies and Peptides with Radiometals. 2.7 Characterization of
Radiolabeled mAbs and Peptides. 2.8 Summary. Acknowledgments. References.
3. The Design of Radiolabeled Peptides for Targeting Malignancies (Leonard
G. Luyt). 3.1 Introduction. 3.2 Peptide Targets. 3.3 Peptides as Cancer
Targeting Agents. 3.4 Multimodality Agents. 3.5 Future Outlook. References.
4. Peptide Receptor Radionuclide Therapy in Patients with Somatostatin
Receptor-Positive Neuroendocrine Tumors (Martijn van Essen, Dik J.
Kwekkeboom, Wouter W. de Herder, Lisa Bodei, Boen L. R. Kam, Marion de
Jong, Roelf Valkema, and Eric P. Krenning). 4.1 Introduction. 4.2
Radiotherapy with 111In-Octreotide. 4.3 Radiotherapy with 90Y-DOTATOC. 4.4
Targeted Radiotherapy Studies with 177Lu-Octreotate. 4.5 PRRT with Other
Somatostatin Analogues. 4.6 Comparison of Different PRRT Studies. 4.7
Comparison with Chemotherapy. 4.8 Options for Improving PRRT and Future
Directions. 4.9 Conclusions. References. 5. Targeted Radiotherapy of
Central Nervous System Malignancies (Michael R. Zalutsky, David A. Reardon,
and Darell D. Bigner). 5.1 Malignant Brain Tumors. 5.2 Rationale for
Locoregional Therapy. 5.3 Targeted Radiotherapy of Brain Tumors. 5.4
Rationale for Tenascin-C as a Target for Radionuclide Therapy. 5.5
Perspective for the Future. Acknowledgments. References. 6.
Radioimmunotherapy for B-Cell Non-Hodgkin Lymphoma (Thomas E. Witzig). 6.1
Introduction. 6.2 Radioimmunotherapy. 6.3 Antibodies Against CD22. 6.4 RIT
Versus Immunotherapy. 6.5 RIT in Rituximab Refractory Patients. 6.6 RIT for
Previously Untreated Patients. 6.7 RIT for Relapsed Large-Cell Lymphoma.
6.8 RIT for Transformed Lymphoma. 6.9 RIT for Mantle Cell Lymphoma. 6.10
Long-Term Results of RIT. 6.11 Risk of Myelodysplasia with RIT. 6.12
Feasibility of Treatment After RIT Failure. 6.13 Combinations of RIT and
Chemotherapy. 6.14 High-Dose RIT with Stem Cell Support. 6.15 RIT for
Central Nervous System Lymphoma. 6.16 Retreatment with RIT. 6.17 RIT in
Children with Relapsed NHL. 6.18 RIT in Patients with Lung Involvement.
6.19 RIT in Patients with Skin Lymphoma. 6.20 RIT in Patients with >25%
Marrow Involvement. 6.21 RIT in Older Patients. 6.22 RIT in Hodgkin's
Disease. 6.23 Viral Infections After RIT. 6.24 Radiation Therapy After RIT.
6.25 Summary. 6.26 Future Directions. References. 7. Radioimmunotherapy of
Acute Myeloid Leukemia (Todd L. Rosenblat and Joseph G. Jurcic). 7.1
Introduction. 7.2 Antigenic Targets. 7.3 Radionuclide Selection. 7.4
Radiolabeling. 7.5 Pharmacokinetics and Dosimetry. 7.6 RIT with b-Particle
Emitters. 7.7 RIT with a-Particle Emitters. 7.8 Summary. References. 8.
Pretargeted Radioimmunotherapy of Cancer (Robert M. Sharkey and David G.
Goldenberg). 8.1 Introduction. 8.2 The Challenge of Improving
Tumor/Nontumor Ratios. 8.3 Pretargeting: Uncoupling the
Antibody-Radionuclide Conjugate. 8.4 Clinical Studies of Pretargeting. 8.5
Prospects for Combination Therapies. 8.6 Future Innovations. 8.7
Conclusions. References. 9. Targeted Auger Electron Radiotherapy of
Malignancies (Raymond M. Reilly and Amin Kassis). 9.1 Introduction. 9.2
Radiobiological Effects of Auger Electrons. 9.3 Selection of an Auger
Electron-Emitting Radionuclide. 9.4 Microdosimetry. 9.5 Molecular Targets
for Auger Electron Radiotherapy of Cancer. 9.6 Small-Molecule Auger
Electron Radiotherapy. 9.7 Summary and Conclusions. Acknowledgments.
References. 10. Viral Introduction of Receptors for Targeted Radiotherapy
(Kathryn Ottolino-Perry and Judith Andrea McCart). 10.1 Introduction. 10.2
Viral Vectors. 10.3 Virally Delivered Receptors. 10.4 Combined Oncolytic
and Targeted Radiotherapy. 10.5 Summary. References. 11. Preclinical Cell
and Tumor Models for Evaluating Radiopharmaceuticals in Oncology (Ann F.
Chambers, Eva A. Turley, John Lewis, and Leonard G. Luyt). 11.1
Introduction. 11.2 Traditional Approaches to Preclinical Evaluation of
Radiotherapeutics. 11.3 Models of Cancer. 11.4 Animal Models for Evaluating
Radiopharmaceuticals: Unresolved Issues and Challenges for Translation.
References. 12. Radiation Biology of Targeted Radiotherapy (David Murray
and Michael Weinfeld). 12.1 Introduction. 12.2 Targeted Radionuclide
Therapy: Concepts. 12.3 Radiation-Induced DNA Damage. 12.4 Cellular DNA
Damage Surveillance-Response Networks. 12.5 Mammalian DNA-Repair Pathways.
12.6 Modes of Cell Death Following Radiation Exposure. 12.7 Conventional
Models for Cell Survival Curves, Fractionation, and Dose-Rate Effects. 12.8
Low-Dose Hyperradiosensitivity-Increased Radioresistance. 12.9 Inverse
Dose-Rate Effects. 12.10 Cross fire. 12.11 The Radiobiological Bystander
Effect. 12.12 The Adaptive Response. 12.13 A Possible Contribution from
Low-Dose Radiobiological Mechanisms to TRT Tumor. Responses?. 12.14 Use of
Radionuclides Other Than b-Particle Emitters. 12.15 Role of Tumor Hypoxia
and Fractionation Effects. 12.16 Summary and Future Directions.
Acknowledgments. References. 13. Dosimetry for Targeted Radiotherapy (Sui
Shen and John B. Fiveash). 13.1 Introduction. 13.2 Basic Concepts of MIRD
Dosimetry. 13.3 Preclinical Dosimetry. 13.4 Clinical Dosimetry Methods.
13.5 Dosimetry for Dose-Limiting Organs and Tumors. 13.6 Conclusions.
References. 14. The Bystander Effect in Targeted Radiotherapy (Carmel
Mothersill and Colin Seymour). 14.1 Introduction. 14.2 Historical Review of
Bystander Effects in the Context of Radiation Damage to Cells. 14.3 New
Knowledge and the Pillars of the Developing New Paradigm. 14.4 Concept of
Hierarchical Levels of Assessment of Targeted Radiation Effects. 14.5 The
New Meaning of the LNT Model. 14.6 Techniques for Studying Bystander
Effects. 14.7 Bystander Phenomena in Targeted and Conventional
Radiotherapy. 14.8. Mechanisms Underlying Bystander Effects and Detection
Techniques. 14.9. The Future. References. 15. The Role of Molecular Imaging
in Evaluating Tumor Response to Targeted Radiotherapy (Norbert Avril). 15.1
Introduction. 15.2 Positron Emission Tomography. 15.3 Response to Cancer
Treatment Including Targeted Radiotherapy. References. 16. The Economic
Attractiveness of Targeted Radiotherapy: Value for Money? (Jeffrey S.
Hoch). 16.1 Introduction. 16.2 Applying Economics in Theory. 16.3 Applying
Economics in Practice. 16.4 The Economic Attractiveness of Targeted
Radiotherapy: the Case of 90Y-Ibritumomab Tiuxetan (Zevalin). 16.5
Conclusions. References. 17. Selected Regulatory Elements in the
Development of Protein and Peptide Targeted Radiotherapeutic Agents (Thomas
R. Sykes and Connie J. Sykes). 17.1 Introduction. 17.2 Administrative and
Organizational Elements. 17.3 Pharmaceutical Quality Elements. 17.4
Nonclinical Study Elements. 17.5 Clinical Study Elements. 17.6 Summary.
Dedication. References. Index.