Systemic Radiotherapy with Monoclonal Antibodies

Almost a century ago Paul Ehrlich introduced the "magic bullet" concept of targeting therapeutic agents to specific tissues in order to reduce systemic toxicity. Due to the advances in hybridoma technology in the 1980s, monoclonal antibodies (MAbs) with their exquisite affinity to tumor antigens have become powerful tools in the treatment of cancer, especially when linked to therapeutic agents such as radionuclides, drugs, toxins, or enzymes. It can now be expected that such agents will lead to new cancer treatments with high therapeutic success rates. However, there are major problems in developing this therapeutic concept to a routine treatment modality. This is partly due to factors such as heterogenous distribution of tumor antigens, insufficient blood supply of tumors, high interstitial pressure, and the large interstitial space that antibodies have to traverse. This book is focused on the development in radio immunotherapy (RIT) using radio labeled monoclonal antibodies as tumoritoxic agents. This area of research has attracted the interest of clinicians and scientists from many different disciplines. It is now clear that the full potential of RIT can only be realized through the concerted efforts of laboratory scientists (molecular biologists, cell physiologists, chemists, radiation physicists, and biologists) and cancer clinicians in nuclear medicine, radiooncology, and internal oncology.

Klappentext

Almost a century ago Paul Ehrlich introduced the "magic bullet" concept of targeting therapeutic agents to specific tissues in order to reduce systemic toxicity. Due to the advances in hybridoma technology in the 1980s, monoclonal antibodies (MAbs) with their exquisite affinity to tumor antigens have become powerful tools in the treatment of cancer, especially when linked to therapeutic agents such as radionuclides, drugs, toxins, or enzymes. It can now be expected that such agents will lead to new cancer treatments with high therapeutic success rates. However, there are major problems in developing this therapeutic concept to a routine treatment modality. This is partly due to factors such as heterogenous distribution of tumor antigens, insufficient blood supply of tumors, high interstitial pressure, and the large interstitial space that antibodies have to traverse. This book is focused on the development in radio immunotherapy (RIT) using radio­ labeled monoclonal antibodies as tumoritoxic agents. This area of research has attracted the interest of clinicians and scientists from many different disciplines. It is now clear that the full potential of RIT can only be realized through the concerted efforts of laboratory scientists (molecular biologists, cell physiologists, chemists, radiation physicists, and biologists) and cancer clinicians in nuclear medicine, radiooncology, and internal oncology.

Inhalt
Monoclonal Antibodies in Tumor Therapy.- Experimental Radioimmunotherapy: Biological Effectiveness and Comparison with External Beam Radiation.- Higher Efficiency of 131I-Labeled Anti-Carcinoembryonic Antigen-Monoclonal Antibody (Fab?)2 as Compared to Intact Antibodies in Radioimmunotherapy of Established Human Colon Carcinoma Grafted in Nude Mice.- Problems and Advances in the Dosimetry of Radionuclide Targeted Therapy.- Minimal Residual Disease: a Target for Radioimmunotherapy with 131I-Labeled Monocloncal Antibodies? Some Dosimetric Considerations.- Optimal Therapeutic Strategies for Radioimmunotherapy.- Two Approaches for Enhancing Radioimmunotherapy: ? Emitters and Hyperthermia.- Can Preirradiation Enhance Tumor Uptake of Radiolabeled Pharmaceuticals? Experimental Data in a Mouse Neuroblastoma Xenograft System.- The Use of Radioimmunotherapy in Combination with Bioreductive Agents.- Treatment of Diffuse Leptomeningeal Malignancy by Intrathecal Injection of 131I-Radioimmunoconjugates.- The Treatment of Patients with Recurrent Malignant Gliomas with Intratumoral Radioimmunoconjugates.- High Dose Radioimmunotherapy in Malignant Lymphoma.- The Use of Epidermal Growth Factor Receptor-425 Monoclonal Antibodies Radiolabeled with Iodine-125 in the Adjuvant Treatment of Patients with High Grade Gliomas of the Brain.