Targeted Radionuclide Tumor 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. 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.

Radioimmunotherapy, also known as systemic targeted radiation therapy, uses antibodies, antibody fragments, or compounds as carriers to guide radiation to the targets. It is a topic rapidly increasing in importance and success in treatment of cancer patients. This book represents a comprehensive amalgamation of the radiation physics, chemistry, radiobiology, tumor models, and clinical data for targeted radionuclide therapy. It outlines the current challenges and provides a glimpse at future directions. With significant advances in cell biology and molecular engineering, many targeting constructs are now available that will safely deliver these highly cytotoxic radionuclides in a targeted fashion. A companion website includes the full text and an image bank.

Nuclear Medicine Therapy presents the state of the art in targeted radionuclide therapy, both in clinical practice and contemporary clinical investigation and trials. With contributions from an internationally-distinguished group of physicians and scientists, the book is devoted entirely to the use of nuclear medicine techniques and technology for therapy of malignant and benign diseases. Individual chapters cover the scientific principles and clinical applications of radionuclide therapy and the state of clinical trials of agents currently under investigation in the therapy of tumors involving virtually every organ system. Due to overlapping interest in techniques, indications, and clinical use, the development of radionuclide therapy attracts considerable input from other medical specialists whose collaboration is essential, including radiation and medical oncologists, hematologists, diagnostic radiologists, hepatologists, endocrinologists, and rheumatologists. And because radionuclide therapy is a rapidly evolving field of nuclear medicine, it is the aim of this volume to appeal to all specialists involved in targeted radionuclide therapy and to contribute to the standardization of the practice globally.

This book reviews locoregional radionuclide cancer therapies (LRCT). Proving an increasingly viable alternative to radiotherapy, radionuclide therapy includes a diversity of choices of well characterized biochemical and physiologic target molecules. The delivery and retention of radionuclides may be monitored by advanced imaging for exact tissue localization and for real-time dosimetry to enable personalized precision medicine. Radiopharmaceuticals in human cancer therapies are typically delivered in systemic routes but can also be designed for locoregional routes to harness pharmacokinetic advantages of higher payload and lower systemic toxicities. This book explores the latest advancements and clinical considerations of the locoregional approach. Throughout the chapters, the clinical and scientific bases of cancer treatment and the locoregional use of radionculides are explored. Mathematical models of radiation dosimetry of locoregional radionculdies on tissues are studied using common models for multiple commercially available radionuclides. Rodent and canine tumor models of LRCT are compared for selected radionuclides and radiopharmaceuticals. The practical aspects of radiopharmaceuticals production, marketing, transport, as well as radiation protection are reviewed. Finally, the combination of LRCT with immunotherapy and other cancer therapies and prospective future use of LRCT are discussed. This is a guide for practicing nuclear physicians, interventional radiologists, radiation oncologists, radiation scientists, veterinarians and oncologists to expand their knowledge base and to prepare for designing locoregional radionuclide cancer therapies in animals and in humans.

The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. This up-to-date, comprehensive book, written by world-renowned experts, discusses the basic principles of radionuclide therapy, explores in detail the available treatments, explains the regulatory requirements, and examines likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the role of the therapeutic nuclear physician in coordinating a diverse multidisciplinary team, which is central to the safe provision of treatment.

This book provides detailed information on therapeutic radiopharmaceuticals and discusses emerging technologies which have potential for broad clinical implementation. Recent advances in molecular biology, radiopharmaceutical chemistry and radioisotope production have stimulated a new era for the use of radiopharmaceuticals for targeted radionuclide therapy (TRT). Emerging clinical trials include use of peptides and monoclonal antibodies radiolabeled with therapeutic radionuclides for cancer therapy. In addition, small molecules are used for the treatment of chronic diseases such as metastatic bone pain palliation and radiation synovectomy of inflammatory joints. In the interventional arena, therapy of primary and metastatic liver cancer and arterial restenosis following angioplasty of both the coronary and peripheral arteries are being explored. Reactor and accelerator production of therapeutic radioisotopes is also integrated into these discussions. The development and use of radiopharmaceutical targeting characteristics required for treatment of specific disease processes and how these are implemented for radiopharmaceutical design strategies are also described. Radiopharmaceuticals for Therapy will benefit audiences in nuclear medicine and radionuclide therapy and will thus prove an invaluable source of up-to-date information for students, radiopharmaceutical scientists and professionals working in the radiopharmacy and nuclear medicine specialties.

Nearly 20 million nuclear medicine procedures are carried out each year in the United States alone to diagnose and treat cancers, cardiovascular disease, and certain neurological disorders. Many of the advancements in nuclear medicine have been the result of research investments made during the past 50 years where these procedures are now a routine part of clinical care. Although nuclear medicine plays an important role in biomedical research and disease management, its promise is only beginning to be realized. Advancing Nuclear Medicine Through Innovation highlights the exciting emerging opportunities in nuclear medicine, which include assessing the efficacy of new drugs in development, individualizing treatment to the patient, and understanding the biology of human diseases. Health care and pharmaceutical professionals will be most interested in this book's examination of the challenges the field faces and its recommendations for ways to reduce these impediments.

The main purpose of this book is to create a reference for the indications, contraindications, patient selection, treatment practice, treatment side effect management, and follow-up of radionuclide treatments. Besides standard methods such as surgery, chemotherapy, radiotherapy, and hormone therapy, newly developed biological treatments, targeted treatments, personalized treatments, external beam radiotherapy, and targeted radionuclide treatments have begun to take their place in professional practice. Nuclear medicine, in addition to its role as a tracer of cancer, also assumes the role of treating with radioactive molecules directed to the cancer it traces. These traceable next-generation radionuclide treatments, whose efficacy and reliability have been proven and where diagnosis, treatment, and follow-up are carried out together, are increasingly included in oncology practice together with the new developed radiopharmaceuticals, ensuring a high rate of damage to cancer cells while protecting the surrounding normal tissues. Molecular cancer treatment will become more effective with individualized next-generation traceable radionuclide treatments, which will be shaped by genetic studies in the future. Radionuclide treatments for many cancer types and benign diseases are presented by experienced nuclear medicine experts in the light of their own experience and case studies, while systemic treatments in common cancer types and side effect management of these treatments are summarized by medical oncologists. This book will be of interest to nuclear medicine physicians as well as oncologists.