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.
Focus on biological effects of targeted radionuclide therapy
Comprehensive presentation of different mechanisms of tumor cell death
Up-to-date presentation of new targeting agents
Summaries of present state of clinical applications of targeted therapy
Introduction of the new concept; Autosensitization during radionuclide therapy
The last three decades have provided opportunities to explore the potential of treating malignant diseases with antibodies or other targeting molecules labelled with nuclides. The expanding array of new targeting molecules (recombinant antibodies or peptides) may increase the therapeutic efficacy. The title of this book "Targeted Radionuclide Tumor Therapy – Biological aspects" was selected to reinforce the concept that a major focus was devoted to understanding the biological effects of targeting and radiation. Furthermore, our rapidly expanding knowledge of low dose-rate effects, different types of cell death, autosensitization 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.
The development of targeted therapy is a true multidisciplinary enterprise involving physician scientists from the fields of nuclear medicine, radiation therapy, diagnostic radiology, surgery, gynaecology, pathology and medical oncology/haematology. It also involves many preclinical scientists working with experimental animal models, immunochemistry, recombinant antibody technologies, radiochemistry, radiation physics and basic cell biology.
It is the ambition of the editors to enable deeper insights in the process of improving targeted therapy. We believe that the time now has come when targeted therapy can soon be added to standard oncology treatment regimens.
List of contributor Preface 1. INTRODUCTION TO RADIONUCLIDE THERAPY; J. Carlsson et al. 2. THERAPEUTICALLY USED ANTIGENS IN RADIOIMMUNOTHERAPY; T. Stigbrand et al. 3. EGFR-FAMILY EXPRESSION AND IMPLICATIONS FOR TARGETED RADIONUCLIDE THERAPY; J. Carlsson 4. TARGETING TUMORS WITH RADIOLABELED ANTIBODIES; T. Stigbrand et al. 5. ANTOBODY FRAGMENTS PRODUCED BY RECOMBINANT AND PROTEOLYTOC METHODS; G. Adams 6. NOVEL ALTERNATIVE SCAFFOLDS AND THEIR POTENTIAL USE FOR TUMOR TARGETED RADIONUCLIDE THERAPY; F. Nilsson 7. PEPTIDES FOR RADIONUCLIDE THERAPY; M. de Jong et al. 8. CHOICE OF RADIONUCLIDES AND RADIOLABELLING TECHNIQUES; V. Tolmachev 9. HIGH-LET-EMITTING RADIONUCLIDES FOR CANCER THERAPY; G. Sgouros 10. TARGETED HIGH-LET THERAPY OF BONE METASTASES; Ø. S. Bruland et al. 11. THE AUGER EFFECT IN MOLECULAR TARGETING THERAPY; H. Lundqvist et al. 12. RADIATION INDUCED CELL DEATHS; D. Eriksson et al. 13. RADIATION INDUCED DNA-DAMAGE/REPAIR AND ASSOCIATED SIGNALING PATHWAYS; B. Stenerlöw et al. 14. RADIATION INDUCED DNA DAMAGE CHECKPOINTS; D. Eriksson et al. 15. CANCER STEM CELLS AND RADIATION; D. Eriksson et al. 16. EFFECTS OF LOW DOSE-RATE RADIATION ON CELLULAR SURVIVAL; J. Carlsson 17. BYSTANDER EFFECTS AND RADIONUCLIDE THERAPY; K. M. Prise 18. ENHANCING THE EFFICIENCY OF TARGETED RADIONUCLIDE TREATMENT; G. Adams 19. LOW DOSE HYPERRADIOSENSITIVITY: A HISTORICAL PERSPECTIVE; B. Marples et al. 20. CLINICAL RADIONUCLIDE THERAPY: A. Scott and S. Lee 21. DEVELOPMENT TRENDS IN TARGETED THERAPY-BIOLOGICAL ASPECTS; T. Stigbrand et al.