In the past nuclear medicine has tended to develop in cycles governed by the development of new radiopharmaceuticals followed or preceded by advances in instrumentation. The development of alternative techniques, such as X-Ray Computer Tomography, NMR Imaging and Ultrasound have also had a stimulating effect and pointed the way to new developments. The development of Positron Emission Tomography, while in itself of limited application because of high costs involved, provided a great deal of information which led to the development of new organ or disease specific, single photon emitting radiopharmaceuticals together with tomographic Gamma cameras, whereby detailed information on the biodistribution of the reagents could be obtained with accurate spatial resolution presented in a form suitable for comparison with the other imaging modalities. This technology, known as Single Photon Emission (Computer) Tomography (SPECT or SPET, as the mood takes you) is now an essential tool in nuclear medicine. The volume presents a basic guideline to the technology involved and discusses the application of the method to the investigation of various anatomical regions of the body. The book is an aide memoire to the routine practitioner and a source of information for other medical specialists. "

Metastases determine malignancy. The main attention so far has been focused upon organ metastases. The molecular mechanisms thereof, while far from being totally elucidated, are increasingly well understood. Modern diagnostic tools now enable detection and precise localization of small lesions. In contrast, our knowl edge and diagnostic capabilities regarding metastatic spread to the'lymphatic system are rather limited. However, there have re cently been a number of interesting advances. It is the aim of this volume to submit these developments to detailed analysis. The therapeutic relevance of enhanced sensitivity in detection of lymph node metastases has to be considered in the light of in creased morbidity versus eventual prognostic improvements by modification of therapy. An interesting concept which might im prove diagnostic accuracy while reducing operative morbidity is the "sentinel node" technique. Surgical standards are lacking, however, and many fundamental questions pertaining to precise lymphatic mapping remain unanswered. Whether the sentinel node concept is of general relevance or whether it is applicable in only a few organs remains to be determined. This book offers intensive discussion of the concept from methodological and tu mor biological viewpoints. World-renowned experts with long term involvement in related basic and clinical research provide the reader with a broad survey of actual knowledge together with a critical appraisal of recent and future developments. We sincerely hope this book succeeds in providing an outlook as a reference for all clinicians on future prospects and serving and researchers in this extremely important field.

The Association Internationale de Recherche sur la Circulation Osseuse, A.R.C.O., was founded in London in December 1989 by a small group of doctors, surgeons and researchers in basic sciences who had been involved for many years in the study of bone circulation and its disorders. They had met several times in Toulouse, during the International Symposia on Bone Circulation held there since 1973 and they wished to carry their contacts further. In founding A.R.C.O., they established as their primary aims the encouragement and furtherance of research, organisation of meetings and promotion of knowledge on the subject. At the present time, the Association has over a hundred members from more than bone tissue twenty countries in Europe, America and Asia. All have the conviction that and its pathology can only be truly known and studied if one has an understanding of its vascular system and the way its circulation functions. This concept, apparently beyond question, has not yet been adopted by all physicians and scientists who are interested in bone. From time to time, one comes across teaching programmes on bone patho logy which make no mention of bone circulation.

In the developed world, images of brain structure are available as an everyday diagnostic aid, and the characteristic appearances of most pathological conditions can be looked up in a textbook. Functional brain imaging is to this day less widely used, partly because most pressing diagnostic questions can be answered by refer ence to the patient's cerebral anatomy, partly for reasons of technical limitations of functional techniques. PET as a technique is sufficiently resource-demanding and complex to inhibit its use as an everyday diagnostic technique. SPECT lacked suitable tracers for many years, and early systems had poor spatial resolution. However, rotating gamma camera technology has advanced to the point where images of the brain of reasonable quality can be obtained at most large hospitals, and practical tracers, particularly of regional cerebral blood flow, are easily avail able. As research advances, clinical applications are emerging. A recent report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology details a number of currently recognised clinical appli cations, some of which are dealt with in this book. Given this recognition, it is increasingly important that clinicians (particularly neuroclinicians, psychiatrists and specialists in cerebrovascular disease), nuclear medicine specialists and physicists acquire an idea of the major applications of the technique, and the research background on which these applications are based."

The application of magnetic resonance spectroscopy (MRS) to the cardiovascular system is a relatively new phenomenon. Its ability to noninvasively examine myocardial metabolism has led to its use to answer basic questions in animal models of normal and diseased myocardium. Extension of these investigations into the realm of human myocardial metabolism has been made possible by the advent of relatively high-field magnets with spectroscopy capabilities and sufficient bore dimensions to allow human studies. While ongoing and future studies promise to enhance our understanding of myocardial metabolism, their success will, in part, depend on a thorough understanding of the technical and biologic aspects of cardiovascular MRS, as well as the current state of research in the many areas encompassed by this discipline. It is with concept that the present monograph has been written. The organization and content should lend this book to both the beginning reader who is interested but not conversant in cardiovascular MRS, as well as to the active investigator who wishes to refer to a volume that deals with the many issues of this field in a concise but complete manner. The monograph is structured with a general overview of the field, followed by a section addressing the technical issues of cardiovascular MRS. The next section is devoted to biologic issues of both normal and abnormal myocardial metabolism, primarily devoted to investigations employing phosphorus-31. This is followed by a section dealing with more specialized issues, generally involving other nuclei such as protons, carbon, and sodium. Finally, the clinical applications of cardiovascular MRS are addressed.

An in-depth introduction to radiotherapy physics emphasizing the clinical aspects of the field. This second edition gradually and sequentially develops each of its topics in clear and concise language. It includes important mathematical analyses, yet is written so that these sections can be skipped, if desired, without compromising understanding. The book consists of seven parts covering basic physics (Parts I-II), equipment for radiotherapy (Part III), radiation dosimetry (Parts IV-V), radiation treatment planning (Part VI), and radiation safety and shielding (Part VII). An invaluable text for radiation oncologists, radiation therapists, and clinical physicists.

It was at Frankfurt/Mainin 1899 that Paul Ehrlich first expounded his famous "site-chain theory" -which described the basic immunological principal of antibody-antigen interactio- on the occasion of the opening of the Institute for Experimental Therapeutics (which was later named after him). Nearly 100 years have passed since, and in retrospect it can be said that the "Ehrlich Era" (first steps in immunology "Magic Bullet" concept) and the "Behring Era" (detection of antibodies and serum therapy) formed the essential basis in the development of immunology. Niels K. Jerne, the former director of the Paul Ehrlich Institute in Frankfurt/Main received, together with Georges Kohler and Cesar Milstein, the Nobel Prize in Medicine 1984. These late successors of Ehrlich and Behring first described the hybridoma technology (in 1975) which enabled one of the most important and revolutionary technological innovations in the field of immunology -the production of monoclonal antibodies. It happens that, the time of the publication of this book, just a decade has passed since the first use of radiolabelled monoclonal antibodies in man (by the Lausanne Group). Over these 10 years a tremendous progress has taken place in the field of immunoscintigraphy: A large panel of highly specific monoclonal antibodies against tumour-associated antigens as well as normal cell compounds have been developed. Enormous progress has been made in the field of radiolabelling -from iodine-131 to technetium-99mor even positron-emittingradionuclides, e. g. iodine-124.

The first of a two volume set, Volume 12 provides a long-awaited compilation of NMR theory to paramagnetic molecules. International experts report the latest developments in NMR methodology as applied to strongly relaxed and shifted resonances, detail the theoretical aspects of paramagnetic shift and relaxation, and discuss the interpretive bases of these molecular properties in relation to the structure and function of various paramagnetic molecules.

It was only in 1980 that the first recognisable magnetic resonance images of the human brain were published, by Moore and Holland from Nottingham University in England. There then followed a number of clinical trials of brain imaging, the most notable from the Hammersmith Hospital in London using a system designed by EMI, the original manufacturers of the first CT machines. A true revolution in medicine has ensued; in only a few years there are thousands of scanning units, and magnetic resonance imaging (MRI) has assumed a central importance in medical investigation. It is an extraordinary fact that within a few years of development, the esoteric physics of nuclear spin, angular momentum, and magnetic vector precession were harnessed to provide exquisite images of living anatomy; modem science has no greater tribute. That indisputable king of neurology and the oldest of recorded conditions, epilepsy, has not been untouched by the new technology; indeed, it is our view that the introduction of MRI of electroencephalography (EEG) in the late has been as important to epilepsy as was that 1930s. Now, for the first time, the structural and aetiological basis of the condition is susceptible to thorough investigation, and MRI can provide structural detail to parallel the functional detail of EEG. MRI has the same potential as had EEG over 50 years ago, to provide a new level of understanding of the basic mechanisms, the clinical features and the treatment of epilepsy.

In recent years there have been tremendous advances in cardiac imaging techniques covering the complete spectrum from echocardiography, nuclear cardiology, magnetic resonance imaging to contrast angiography. With respect to these noninvasive and invasive cardiac imaging modalities, marked technological developments have allowed the cardiologist to visualize the myocardium in a far more refined manner than conventional imaging was capable of. Echocardiography has extended its domain with intravascular ultrasound, cardiovascular nuclear imaging has added positron emission tomography to its line of research, magnetic resonance imaging has been broadened with magnetic resonance angiography and spectroscopy, and finally contrast angiograp hy has widened its scope with excellent quantitation programs. For all these imaging modalities it is true that the application of dedicated quantitative analytic software packages enables the evaluation of the imaging studies in a more accurate, reliable, and reproducible manner. It goes without saying that these extensions and achievements have resulted in improved diagnostics and subsequently in improved patient care. Particularly in patients with ischemic heart disease, major progress has been made to detect coronary artery disease in an early phase of the disease process, to follow the atherosclerotic changes in the coronary arteries, to establish the functional and metabolic consequences of the luminal obstructions, and to accurately assess the results of interventional therapy.

Scintigraphic imaging with radiolabeled blood elements has continued to be a useful diagnostic modality. The major trust of recent investigation has been in simplifying labeling techniques and developing new agents that will label blood elements selectively in vitro. The VI Symposium of the International Society of Radiolabeled Blood Elements was held in Barcelona (Spain) during November 23 to 27, 1992.The conference was sponsored by the NATO Scientific Affairs Division, the USA Department of Energy and the Spanish National Health Service. This monograph comprises articles that represent most of the 85 papers (70 oral and 15 posters) presented during the symposium. The meeting was attended by 110 investigators hailed from 21 countries. Although lllIn-oxine and 99mTc-HMPAO remain the choice agents for labeling blood components for routine applications, there was heavy emphasis on developing new labeling agents that will either simplify the in vitro labeling procedure, or, even better, will label blood components selectively in vivo, by injecting the radioactive agents directly into patients. The degree of success in imaging target lesions in humans by using these agents has been excellent.

The clinical use of nuclear cardiology for the assessment of myocardial ischemia continues to grow at an unprecedented rate. Part of the reason for this growth is the technical advances in single photon emission computerized tomography (SPECT). SPECT has been shown to provide high contrast images superior to planar imaging techniques. An important and recent technical advancement in SPECT has been ECG-gated myocardial perfusion SPECT to generate simultaneous myocardial perfusion and function information from a single study. Automated, quantitative techniques have facilitated the widespread application of this breakthrough. Another recent advancement has been the use of attenuation correction techniques to help remove the effects of the physical phenomena that degrades the visual and quantitative accuracy of SPECT images. Another reason for the growth of the clinical use of nuclear cardiology is the large body of published evidence documenting the effectiveness of SPECT techniques for assessing myocardial ischemia, myocardium at risk, viable myocardium and stunned or hibernating myocardium. These assessments have been shown to be important not only in diagnosis but also in prognosis. This book is divided into three major sections, each addressing the important topics of nuclear cardiology. The first section is a that have led to the clinical success description of the technical aspects of state-of-the-art myocardial perfusion SPECT imaging. This section deals with the radionuclides, instrumentation, image acquisition and analysis, interpretation and quantification techniques used in the most progressive nuclear cardiology clinics.

Can drug development and evaluation be improved by the use of positron emission tomography (PET)? PET is now well established and many PET centres participate in networks that warrant the quality of their research. PET allows one to follow the effect of a drug on a variety of patients' metabolic parameters. In addition, PET may be used to follow the fate in vivo of a compound, allowing visualisation of its binding to specific receptors and a direct study of the mechanism of drug action in normal and pathological situations. The book shows the fields in which PET offers new and unique information for the development of drugs (conception, toxicity, pharmacokinetics and metabolism, clinical research, and relations between clinical and biological effects) and evaluates fields in which PET may shorten the development time of drugs. Audience: Professionals in the pharmaceutical industry in all areas of drug discovery and pharmacology, pre-clinical testing, pharmacokinetics and metabolism, clinical evaluation, registration and regulatory affairs. Government health authority representatives who assess data and documentation on new drug development and radiopharmaceuticals. Academic experts concerned with any of these areas.

Among the readily available -emitting radionuclides, the nuclides of iodine have the greatest versatility in labeling both the hydrophilic and the lipophilic compounds that are used in biology and medicine. Biologically important micrmolecules, semimacromolecules, and macromolecules have been identified which, after iodination, almost maintain the same molecular configuration and similar biologic specificity as those of the parent molecules. The multiple techniques for iodination and the clinical use of iodinated products have made possible the present status of the development of diagnostic nuclear medicine. 125r, with a half-life of 60 days, has a crucial role in competitive protein-binding studies. 131r is useful for measuring thyroid uptake, for the diagnosis of thyroid carcinoma and metastasis, and for therapy. 1nr , with a reasonably shorter half-life, is almost ideal for thyroid workup and for a few useful labeled radiopharmaceutical. Although ~c is used more widely in diagnostic procedures, the radionuclides of iodine will always have a major role in biology and medicine. A considerable amount of information is scattered in the literature regarding the chemistry of radioiodination and the mechanism of tracer localization in cells and tissues. Labeled peptides, proteins, and antibodies are extensively used for protein turnover studies, receptor binding and tumor imaging studies, and radioimmunoassay. The general trend in the use of tracers in clinical nuclear medicine has been an evolution from 3H, 14C, 11C, and 13 to 125 , 131 and 123r to ~c and 111rn.

The philosophy of this NATO Advanced Research Workshop and the monograph it has yielded is that if you put a small number of very talented and creative scientists of different backgrounds and documented accomplishments together in a cloistered place for a few days to consider a very important and timely topic, many new ideas will be generated. The keynote of this conference was the Future. By this we mean the expected future developments of highly reliable sequential quantitative measurements of atherosclerotic plaque size and components in living human subjects. Some of the best minds and the most experienced and talented individuals at the leading edges of imaging of arteries were involved; some of the best scientists and students of the atherosclerotic plaque and its components participated; and some of the leading investigators of the cell biology or, as we call it in the USA, the pathobiology of atherosclerosis, contributed important new information. All of these individuals were actively involved in the conference and each obviously had carefully prepared and was able to communicate effectively.

The primary purpose of this book is to bridge the gap be tween the practice of clinical medicine and diagnostic radi ology. It is intended primarily for utilization by medical students in training and by nonradiologist physicians. In this world of rapidly expanding knowledge in the many specialties of medicine, it is becoming increasingly difficult for many physicians to stay abreast of the newer and constantly changing modalities of diagnosis as well as the therapeutic regimens of the common as well as the less common disease processes within their realm of practice. This book will enable the busy clinician to utilize the consultative services offered by his or her colleagues in diagnostic radiology with maximum effectiveness. The most common clinical applications of the more recent imag ing modalities (i. e. , nuclear medicine, ultrasound, comput erized tomography, and magnetic resonance imaging) have been categorized and condensed into a format that will be both comprehensible and useful on a daily basis for those physicians routinely requesting these diagnostic examina tions for their patients. For simplicity, the book is divided, whenever feasible, into organ systems and subdivided into the multiple classifications of pathologic states (i. e. , con genital, trauma or iatrogenic, inflammatory, and neo plasm). In addition, there are brief comments related to the vii specific advantages and disadvantages as well as the cost effectiveness of each modality.

Twenty years ago, the enzyme superoxide dismutase which uses the superoxide radical anion as its specific substrate was reported. With this discovery was born a new scientific field, in which oxygen, necessary for aerobi c 1 ife on thi s planet, had to be cons i dered also in terms of its toxicity and stresses. This stimulated the search for knowledge of active oxygen species in biology and medicine. Superoxide and other reactive oxygen species are now implicated in many disease processes. Major advances have been achieved during these past years with respect to free radical generation and mechanisms of free radical action in causing tissue injury. In parallel, the possibil ity of influencing free radical related disease processes by antioxidant treatment was studied in various in vitro and in vivo systems. This was the unique theme of a conference organized in Paris by the Society for Free Radical Research (December 9-10, 1988) which brought together experts from basic sciences and clinicians in order to evaluate the current status of antioxidant therapy. The conference emphasized fundamental processes in antioxidant action. Among the major topics were superoxide dismutase (SOD) and low molecular weight substances with such activity, called SOD mimics. Other antioxidant enzymes were also considered. Antioxidant vitamins, in particular vitamins E and C, other naturally occurri ng antioxidants and vari ous synthet i c antioxidants were included in the presentations as there is now a rapidly developing series of compounds with potentially interesting clinical applications.

Oncological surgeons are often requested in their clinical practice to identify and manage uncommon and complex situations. It is therefore of the utmost importance that they are well aware of the most recent technological evolutions, in order to achieve the best possible results in term of oncological outcome, with a concern on quality of life and economical issues. Furthermore, new techniques can give a fundamental contribution in overcoming the limitations of standard approaches.

An essential aim of this book is to underline the great importance and the need of an effective coordination of multi-disciplinary care among surgeons, medical oncologists, radiation therapists, plastic surgeons and ancillary services, in order to optimise patient outcome.

With the present Badgastein Symposium "Radioactive Isotopes in Clinical Medicine and Research" we have now had 40 years of an uninterrupted series of Badgastein meetings on nuclear medicine, since the first one took place in January 1954. We believe that this anni versary is worth mentioning. The 21 st symposium proved again to offer a representative cross section through the current topics of scientific interest of nuclear medicine. The general theme of research in nuclear medicine has shifted from the spectacular new developments which were so often reported in the first symposia to a less spectacular, albeit equally important period, which may best be characterized by validation and standardization. While this may not be as exciting as we would like it to be, it is nevertheless vital for nuclear medicine to maintain and improve its standing amongst the other specialties of medicine which draw upon the services that nuclear medicine offers."

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.

Bone Metastases brings together the many recent developments that are gradually improving the prospects for patients with secondary involvement of the skeleton in a primary cancer elsewhere. The morbidity from bone metastases is extensive, and the palliative and supportive treatment that sufferers require for many months or even years constitutes a major health problem. A multidisciplinary approach is essential since a variety of specialists are involved: radiation and medical oncologists, general and orthopaedic surgeons, general physicians, radiologists and nuclear medicine physicians, symptom control and terminal care specialists. The book's editors, themselves authorities in the fields of oncology and bone disease respectively, have brought together experts from all these disciplines to provide comprehensive coverage of metastatic bone disease. They cover the biology and pathophysiology, hypercalcaemia, imaging, assessment of response to treatment, types of treatment (systemic, radiotherapy, surgery), and symptomatic and supportive care. Particularly new approaches included are magnetic resonance imaging, the assessment of skeletal response and isotope therapy.

Blood stem cell transplantation has become an established therapeutic option in the treatment of malignant diseases. At the same time molecular therapeutic approaches (i.e. gene therapy) are promising alternatives to the classical treatment of cancer. The proceedings give an overview of the biology of hematopoietic progenitor cells, peripheral stem cell transplantation in patients with hematological malignancies, recent developments in molecular diagnosis and gene therapeutic concepts, and show that successful future developments require cooperative research connecting basic science with clinical application.

For this Workshop, the organizers have attempted to invite experts from all known centers which are engaged in neutron beam development for neutron capture therapy. The Workshop was designed around a series of nineteen invited papers which dealt with neutron source design and development and beam characterization and performance. Emphasis was placed on epithermal beams because they offer clinical advantages and are more challenging to implement than thermal beams. Fission reactor sources were the basis for the majority of the papers; however three papers dealt with accelerator neutron sources. An additional three invited papers provided a summary of clinical results of Ncr therapy in Japan between 1968 and 1989 and overviews of clinical considerations for neutron capture therapy and of the status of tumor targeting chemical agents for Ncr. Five contributed poster papers dealing with NCT beam design and performance were also presented. A rapporteurs' paper was prepared after the Workshop to attempt to summarize the major aspects, issues, and conclusions which resulted from this Workshop. Many people contributed to both the smooth functioning of the Workshop and to the preparation of these proceedings. Special thanks are reserved for Ms. Dorothy K.

The rapidly growing area of nuclear medicine imaging receives only limited attention in broad-based medical dictionaries. This encyclopedic dictionary is intended to fill the gap. More than 400 entries of between one and three paragraphs are included, defining and carefully explaining terms in an appropriate degree of detail. The dictionary encompasses concepts used in planar, SPECT, and PET imaging protocols and covers both scanner operations and popular data analysis approaches. In spite of the mathematical complexities in the acquisition and analysis of images, the explanations given are easy to understand and many helpful concrete examples are provided. The book will be ideal for those who wish to obtain a rapid grasp of a concept beyond a definition of a few words but do not have the time to search the reference literature. The almost tutorial-like style accommodates the needs of students, nuclear medicine technologists, and varieties of other medical professionals.

During the last decade many significant advances have been made in the in vivo diagnosis of disease. An area of partic- ular success has been the application of nuclear medical procedures to the detection of cardiac disease. Not only is it possible to detect infarction or ischemia by scintigraphic techniques but by the use of labelled metabol- ites and analogues of potassium the viability of myocardial tissue can be evaluated. The efficiency of the heart pump can be calculated and wall motility observed in one simple proce- dure. The use of ultra short life radionuclides has made the evaluation of rapid changes in myocardial function feasible. Altogether a broad and impressive diagnostic package. In this volume up-to-date reviews of all of the available techniques have been collected including methods which are still in the development phase. There is an inherent emphasis on European experience in Nuclear Cardiology which is then placed in context with world wide experience in the field. This volume will be of interest to all concerned with cardiac diseases and we hope that it will serve to stimulate further developments in the future. H.J. Biersack, Bonn P.H. Cox, Rotterdam VIII CONl'RIBUTORS Bauer, R. - Nukleanredizinisdl.e Klinik und Poliklinik redl.ts der Isar der Tedlnisdl.en Universitat Mlinchen, FRS. Biersack, H.J. - Institut fur klinisdl.e und experimentelle Nukleanredizin der Universitat Bonn, FRG. Breuel, H.P. - Degussa Phanna Horrburg, Frankfurt 1, FRG. Cox, P .H. - Department of Nuclear Hedicine, Rotterdamsdl. Radio-Therapeutisdl.