This book is a compilation of the invited papers, which were presented at the Fourth European Symposium on Radiopharmacy and Radiopharmaceuticals, which was held in Baden, Switz- land, 1-4 May, 1991. The First and Third Symposia on Radiopharmacy and Radiopharmaceuticals (Elsinore, Denmark, 1983, 1987) concentrated on the safety and efficacy of radiopharmaceuticals, whereas this Fourth Symposium to some extent followed up the subject of the Second Symposium (Cambridge, UK, 1985): recent developments in radiopharmacy and current research on radiopharmaceuticals. The symposium was organized by the Radiopharmacy Group of the Swiss Society of Medical Radiology (Section Nuclear Medicine) under the auspices of the task group on radiopharmaceu- cals of the European Association of Nuclear Medicine (EANM). The organizing committee consisted of the cochairmen Drs. P.A. Schubiger (Paul Scherrer Institute (PSI), Villigen) and G. Westera (University Hospital, ZiJrich) and the members H.-F. Beer, P. Bl~iuenstein, P. Hasler (all PSI) and H. M~icke (Cantonal Hospital, Basel). The subjects of this Symposium ranged from isotope production to clinical testing of radioph- maceuticals, including the organisational prerequisites. In addition, the development of new radiopharmaceuticals and of PET radiopharmacy, and the concomittant ongoing evolution of regulatory guidelines by national (various European countries, USA) and international (EC) authorities, induced us to honor the vivid interest in this subject and to make it an important part of this symposium.

The publication of this volume, which is based upon presentations made to the Third European Symposium on Radiopharmacology at Noordwijkerhout, April 22 - 24, 1982, is indicative of the continued interest in this sub-branch of Nuclear Medicine. The transactions of the first two meetings were published as Progress in Radiopharmacology, Volumes 1 and 2 by Elsevier/North-Holland Bio medical Press. We are particularly pleased to have reached an agreement with Martinus Nijhoff Publishers to include Progress in Radiopharmacology 3 in the series Developments in Nuclear Medicine. This not only ensures the continuity of the series but by including it in a series of Nuclear Medical Monographs the availability of the text to more general readers, for background information, is greatly enhanced. As with the previous two volumes each of the three topics has been so treated as to relate the biodistribution of the radiopharmaceuticals to normal and pathophysiological conditions to provide background information for the practising nuclear medical specialist. Special attention has been given to European activities but these have been clearly placed in context in relation to developments from outside Europe. The Third European Symposium on Radiopharmacology was held under the auspices of the European Joint Commitee on Radiopharmaceuticals of the European Nuclear Medicine Society and the Society of Nuclear Medicine Europe. Solco Nuclear, Basle, provided both financial and material support and I would like to thank Dr M. de Schrijver, Mr. I. Waser and Mrs. E. Rufenacht for their continued help and encouragement.

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.

This volume is based upon presentations made to the 4th European Symposium on Radiopharmacology which was held under the auspices of the European Joint Committee on Radiopharma ceuticals (ENMS / SNME) in Athens from March 28 - 31, 1984. The Medical Insurance Foundation of the National Bank of Greece (TYPET) sponsored this meeting and the Joint Committee would like to express their gratitude to the local organising committee: G. Limouris, M. Pierroutsakou, A. Sarris, A. Tzoulis and C. Binas. A word of thanks also to Mrs. Tineke Busker who prepared the camera ready copy. The meeting reflects the continuing and growing interest in biodistribution and factors which can influence bio distribution in the clinical situation. The choice of sub jects, respiration, cerebral function, biodistribution and metabolism complement earlier volumes in this series and reflect European interests in these areas. P.H. Cox Rotterdam, April 1985 VII CONTENTS Foreword P.H. Cox v Contributors XI I. THE RESPIRATORY SYSTEM Physiology and pathophysiology of the respiratory system J. Roth, E. Henze, W.E. Adam 3 Generator-produced Krypton-81m in gas and liquid phases for medical applications M. Guillaume, N. Garzaniti, H. Zicot, T. Khuc, P. Bartsch 23 Noble radionuclides for lung ventila tion studies I. Bofilias 49 Radioaerosols in nuclear medicine M. Pillay, B. Shapiro, P.H. Cox 57 99m A dry aerosol of Tc -albuminmilli micro spheres for lung ventilation scintigraphy: preparation, inhalation apparatus and examples of clinical results P. Angelberger, I. Zolle, A. Strigl, H. Kahn, A. Mostbeck, W.

A comprehensive, authoritative and up-to-date reference for the newcomer to radiopharmaceuticals and those already in the field. Radiopharmaceuticals are used to detect and characterise disease processes, or normal biological function, in living cells, animals or humans. Used as tracer molecules, they map the distribution, uptake and metabolism of the molecule in clinical studies, basic research or applied research. The area of radiopharmaceuticals is expanding rapidly. The number of PET centers in the world is increasing at 20% per year, and many drug companies are utilising PET and other forms of radiopharmaceutical imaging to evaluate products. * Readers will find coverage on a number of important topics such as radionuclide production, PET and drug development, and regulations * Explains how to use radiopharmaceuticals for the diagnosis and therapy of cancer and other diseases * The editors and a majority of the contributors are from the United States

Radiophannaceutical research has recently undergone a major change in direction. In past years it has been concerned mainly with the development of perfusion tracers, the biodistribution of which reflect the regional blood flow to areas of major organs such as the heart and brain. However, a major new direction of interest now lies in the development of receptor-binding radio-tracers which can be used to perform in-vivo characterisation of diseased tissues and it is likely that much of the future research in this field will follow this direction. The difficulties in developing such tracers are considerable. The researcher must first identify a promising target for radiopharmaceutical development. High specific activity radioactive molecules must be designed and synthesised which will both bind to the target receptor with high affinity, and also have the physicochemical characteristics which will allow them to reach the target site in sufficient quantity while at the same time showing minimal uptake in non-target tissues. Thus the knowledge base required for radiophannaceutical development has now expanded beyond the limits of radiopharmaceutical chemistry to include aspects of biochemistry, molecular biology and conventional drug design. The portfolio of basic knowledge required to support current radiopharmaceutical development is changing and scientists working in this arena need to be trained in this regard. At the same time, the very latest developments in the field need to be communicated to the scientific community in order to stimulate the advancement of this exciting new direction of research.

This publication contains a collection of 22 manuscripts by authors invited to write review articles. They are based on lectures presented on the First and Second Training Course in Radiopharmacy and Radiopharmacology. These courses were organized under the auspices of the "Joint Committee on Radiopharmaceuticals" of both European Societies of Nuclear Medicine (ENMS and SNME) and were sponsored by the European Society of Nuclear Medicine (ENMS). Recent developments in radiopharmacy and radiopharmacology have been very complex; they cannot be overlooked by the medical staff in nuclear medical departments. This book has been written to provide access to recent research and to practical daily routine in patients' investigations. It provides a wide-ranging and topical overview of radiopharmacology in­ cluding chapters on basic chemistry and physics, incorporation dosimetry, interference of drugs in radiopharmacokinetics, legal aspects and stable isotope-labelled pharmaceuticals. Style of presentation is not uniform. Par­ tial overlapping concerning the content of papers has not been avoided in order to ensure different views and aspects of the same subject. We hope that the interdisciplinary approach will be stimulating and thought-provok­ ing for the reader. Consequently, this book is designed for specialists work­ ing in nuclear medical centres which involve different disciplines such as pharmacists, radiochemists, physicists, biochemists, biologists, mathemati­ cians, electronic engineers, physicians with different specialities, and tech­ nicians.