Targeted Radionuclide Tumor Therapy: Biological Aspects

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Torgny Stigbrand, Jorgen Carlsson, Gregory P. Adams
Springer Science & Business Media, Sep 1, 2008 - Medical - 402 pages
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The last three decades have provided opportunities to explore the potential of treating malignant diseases with antibodies or other targeting molecules labelled with nuclides. While considerable advances have been reported, there is still a signi- cant amount of work left to accomplish before our ambitions can be achieved. It now seems timely to review the accomplishments achieved to date and to clarify the challenges that remain. The choice of radionuclide, the conjugation p- cedure employed, and the selection of suitable targets were early issues that were faced by our field that still persist, however we can now tackle these obstacles with significantly better insight. The expanding array of new targeting molecules (recombinant antibodies, peptides and agents based upon alternate scaffolds) may increase the therapeutic efficacy or even modify the radiation sensitivity of the targeted tumor cell. The title of this book “Targeted Radionuclide Tumour Therapy – Biological Aspects” was selected to reinforce the concept that a major focus of this volume was devoted to understanding the biological effects of targeting and radiation. These important issues have not previously been the primary focus in this context. Furthermore, our rapidly expanding knowledge of different types of cell death and the increasingly likely existence of cancer stem cells suggests to us that even more efficient approaches in targeting might be possible in the future.
 

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Contents

Introduction to Radionuclide Therapy
1
Therapeutically Used Targeted Antigens in Radioimmunotherapy
12
EGFRFamily Expression and Implications for Targeted Radionuclide Therapy
25
Targeting Tumours with Radiolabeled Antibodies
59
Antibody Fragments Produced by Recombinant and Proteolytic Methods
77
Novel Alternative Scaffolds and Their Potential Use for Tumor Targeted Radionuclide Therapy
89
Peptides for Radionuclide Therapy
117
Choice of Radionuclides and Radiolabelling Techniques
145
Radiation Induced DNADamageRepair and Associated Signaling Pathways
249
Radiation Induced DNA Damage Checkpoints
267
Cancer Stem Cells and Radiation
285
Effects of Low DoseRate Radiation on Cellular Survival
294
Bystander Effects and Radionuclide Therapy
311
Enhancing the Efficiency of Targeted Radionuclide Therapy
321
Low Dose HyperRadiosensitivity A Historical Perspective
329
Clinical Radionuclide Therapy
348

HighLETEmitting Radionuclides for Cancer Therapy
175
Targeted HighLET Therapy of Bone Metastases
181
The Auger Effect in Molecular Targeting Therapy
195
Radiation Induced Cell Deaths
215
Developmental Trends in Targeted Radionuclide Therapy Biological Aspects
387
Index
399
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