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."

This book is based on a series of lectures given by an international team as part of a course on Bone Scintigraphy organized by the Boerhaave Committe for Postgraduate Medical Education (Leiden, January 1980). Bone scintigraphy and the use of radionuclide tracers in the investi gation of skeletal pathology has developed into a subject of its own. Significant advances in instrumentation, radiopharmaceuticals and data analysis has considerably widened the scope of clinical application. Beyond the important area of sensitive detection of malignant involve ment of the skeleton, major strides are being made in the investigation of benign bone disease and its metabolic aspects. The structure of this Boerhaave Course reflects this change, with considerable emphasis being given to the discussion of recent methods for tracer uptake quantitation, the discussion of inflammatory osseous disease, benign pathology in general and the investigation of metabolic bone disease. As a clinical tool, bone scintigraphy is present today in most if not all general and regional hospital institutions. It is a technique in demand by genera1 interns, surgeons, radiologists, paediatricians, oncologists and radiotherapists. New areas of application are being evaluated and to some extent consolidated. These include the difficult orthopaedic issues of bone avascularity, prosthesis loosening, infection and non-apparent fractures. A range of new techniques are available and applied to the follow-up of osteomalacia, osteoporosis, osteodystrophy and other con ditions where a more objective and even preferably a numerical approach is being explored."

Proceedings of the 9th Conference, Washington D.C., 10-14 June 1985 Sponsored by the Clinical Center and the Fogarty International Center of the National Institutes of Health, Bethesda, Maryland, USA

A critical phase in coronary heart disease, unstable angina, is thoroughly discussed in contributions by well-known experts. Since myocardial infarction still belongs to the main causes of death, this topic is highly relevant for the present research and possible future treatment of coronary heart disease. The major recent advances made in the pathophysiology, diagnosis and therapy of unstable angina are reported in depth.

Advances in molecular biology describing important enzyme systems involved in drug conjugation and deconjugation reactions and recent work indicating the importance of drug and xenobiotic conjugates as transport forms of biologically active compounds are reviewed comprehensively. Part One describes molecular events associated with the expression and regulation of transferases and hydrolases involved in Phase II drug conjugation and deconjugation. Part Two deals with the regulation of Phase II conjugation, and Part Three reviews critically the importance of drug conjugates in pharmacology and toxicology. This volume is an up-to-date source of information on this topic and will be of broad interest to pharmacologists and toxicologists.

This volume is based on a series of lectures delivered at a one-day teach ing symposium on functional and metabolic aspects of NMR measure ments held at the Middlesex Hospital Medical School on 1st September 1985 as a part of the European Nuclear Medicine Society Congress. Currently the major emphasis in medical NMR in vivo is on its poten tial to image and display abnormalities in conventional radiological im ages, providing increased contrast between normal and abnormal tissue, improved definition of vasculature, and possibly an increased potential for differential diagnosis. Although these areas are undeniably of major importance, it is probable that NMR will continue to complement con ventional measurement methods. The major potential benefits to be de rived from in vivo NMR measurements are likely to arise from its use as an instrument for functional and metabolic studies in both clinical re search and in the everyday management of patients. It is to this area that this volume is directed."

In 1980 the Internal Emitters Committee of EULEP organised a symposium in Rotterdam on Bone and Bone Seeking Radionu cI ides: Their Physiology, Dosimetry and Effects. The speakers for this meeting, mostly from EULEP associ ated laboratories, were chosen to review this field of scientific research mostly for the benefit of interested scientists who were not actively researching with bone seeking radionuclides. This meeting was a success and its proceedings were subsequently published in the form of a book by the Commission of the European Communities, reflecting the great importance that both EULEP and the Radiologi cal Protection Programme of the Commission of the European Communities attaches to the study of radionuclides that deposit in bone. The Metals in Bone symposium in Angers was intended to serve a different function from that of the meeting held in Rotterdam in that, while these proceed ings will certainly be of interest to non-involved scientists, the meeting was intended to be of most benefit to those actively researching the metabolism and effects of bone-seeking metals. Moreover, in an attempt to increase the value of its discussions and the number of interested and participating scientists, the remit of the meeting was broader and set to include papers on stable as well as radioactive metals."

Each volume in the "Atlases of Clinical Nuclear Medicine" covers one anatomic region or system. Each atlas is extensively illustrated with superb quality images and reveals the spectrum of normal scintigraphic findings as well as examples of both common and unusual conditions. Detailed figure legends describe the findings within each image, and most discuss the image's important teaching point. The text, which is descriptive yet concise, covers such topics as procedure technique, dosimetry, physiology, and scan interpretations. Selected Atlases of Bone Scintigraphy is comprised of four individual atlases in the areas of 1) Skeletal Trauma 2) SPECT Cross Sectional Anatomy of the Normal Spine, Pelvis, Hips, and Skull 3) SPECT Quality control 4) Normal Bone Scintigraphy and Indium-11 White Blood Cell Scintigraphy in Porous Coated Hip Prosthesis

During the past decade Positron Emission Tomography (PET) has turned from a highly sophisticated tool developed for basic research in neurology and cardiology into an advanced nuclear medicine imaging technique ready for routine use. Along with remarkable technical improvements, an overwhelming number of PET studies has been published covering not only scientific but also relevant clinical problems. Due to this rapid development, comprehensive information about the current status of 'clinical' PET is lacking. In this book the applications of PET in neurology, cardiology and oncology are discussed in separate sections. In each section, following an introduction reviewing the present clinical demands, special diagnostic problems and their possible solution by PET are addressed. Results of conventional scintigraphic techniques are also mentioned, and compared with PET. In the last section, technical aspects (e.g. instrumentation, software) are presented, including statements of representatives of leading manufacturers in the field. Clinical PET provides a critical overview of relevant applications of PET for all those who are starting to run a PET facility or are planning to do so. The book is also dedicated to interested clinicians who are willing to utilize the diagnostic potential of PET.

The contents of this volume are based upon presentations made to the Second European Symposium on Radiopharmacy and Radiopharmaceuticals which was held in St. Catharine's College Cambridge in March 1985. This meeting was organized by the Radiopharmacy Group of the British Nuclear Medicine Society under the auspices of the European Joint Committee on Radio pharmaceuticals of the ENMS / SNME. The Joint Committee acknowledges the special effort which was made by the local organizers to prepare this meeting the quality of which is undoubtedly reflected in the proceedings. The wide ranging aspects of Radiopharmacy are reflected in this volume which not only deals with specialized topics, such as aerosols and biodistribution studies, but which also deals with the professional aspects of Radiopharmacy Practice. We are of the opinion that this book complements earlier publications to give an ongoing picture of the practice of Radiopharmacy and the state of the art in Europe. As well as acknowledging the contribution of the British Radiopharmacists I would also mention the support of my co chairman Prof. Dr M.G. Woldring, the members of the Joint Committee and last but not least Mrs. M. Busker, who prepared the camera ready copy. P.H. Cox Co-ordinating Chairman European Joint Committee on Radiopharmaceuticals Rotterdam XI CCNrRIBUTORS Anderson, M.L. - Pharnacy department, London Hospital London, UK. Angelberger, P. - Osterreichische Forschungszentrum Seibersdorf GmbH, Wien, Austria. Claessens, R.A.M.J. - Department of Nuclear Medicine, St. Radboud Ziekenhuis, Nijrnegen, The Netherlands."

Radiophannaceuticals labeled with short-lived radionuclides are utilized to unravel biochemical processes, and to diagnosis and treat diseases of the living body are-developed through extensive evaluation in ~iological models. 'fhC first attempt to compile information was a volume entitled ANIMAL MODELS IN RADIOTRACER DESIGN that was edited by William C. Eckelman and myself in 1983. The volume had a focus on the animal models that investigators were using in order to design radiotracers that displayed in vivo selectivity as measured by biodistribution and pharmacokinetic studies. A concern in the early days of nuclear medicine was species differences. Often a series of labeled compounds were evaluated in a several different animal models in order to gain confidence that the selected radiotracer would behave appropriately in humans. During the past 12 years there have been remarkable advances in molecular genetics, molecular biology, synthetic radiopharmaceutical chemistry, molecular modeling and visualization, and emission tomography. Biological models can now be selected that are better defined in terms of molecular aspects of the disease process. The development of high resolution PET and SPET for clinical applications facilitates the development of new radiopharmaceuticals by the use of models to quantitatively evaluate drug effects, and progression of disease, and hence to arrive at better diagnosis and treatments for animals and humans. With these advances there is an effective use of biological models, and the refinement of alternatives for the development of new radiophannaceuticals.

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 book was conceived by Professor K.H. Ephraim, the former director of the Institute for Nuclear Medicine of the University Hospital of Utrecht. Unfortunately, due to a serious illness, he was not able to finish the work he started. He is, however, very pleased to know that the book is, nevertheless, being published. In principle the volume consists of two parts. The first is dedicated to basic science and technology in nuclear medicine. It provides the data which are necessary to a clear understanding of the possibilities and limitations of investigations which make use of radioactive materials. The second part of the book covers those disciplines in medicine in which nuclear medicine can be of help in solving certain clinical problems. Each chapter can be read separately, even without thorough knowledge of the first part of the book. The contributors to this book come from both Europe and North America. Each of them has written his chapter out of long-standing personal interest in his particular field of nuclear medicine. This book will be of value to a wide variety of professionals. It is of interest not only to clinicians of various specialties, but also to diagnostic professionals, i.e. radiologists and nuclear medicine clinicians. Last but not least it will be of use to physicians in training."

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.

The NATO Advanced Study Institute (ASI) on Physics and Engineering of Medical Imaging has addressed a subject which in the wide area of biomedical technology is one of those which are showing greater impact in the practice of medicine for the ability to picture both Anatomy and Physiology. The information and accuracy obtained by whatever imaging methodology is a complex result of a multidisciplinary effort of several sciences such as Physics, Engineering, Electronics, Chemistry, Medicine, etc ... Development has occurred through work performed in different environments such as basic and applied research laboratories, industries and clinical centers, with the aim of achieving an efficient transfer of know-how and technology for the improvement of both investigation possibilities and health care. On one hand, such an effort requires an ever-increasing committment of human and financial resources at research and industrial level, and, on the other, it meets serious difficulties in recruiting the necessary human expertise oriented to this technology which breaks with the tradi tiona I academic borders of the single disciplines. Furthermore, the scientific community is continually dealing with the problem of increasing the performance and, at the same time, complexity and costs of instruments, applying more and more sophisticated technology in an effort to meet the demand for more complete and accurate clinical information. The scientific program of this ASI and the qualification of the authors reveals the intrinsic complexity of the development process of the Imaging methodologies.

Conventional nuelear medieine proeedures study the dis- tribution of radiolabelled eompounds (radiopharmaeeutieals) in the body under physiologieal as well as under pathologieal eonditions. Beeause of their ability to visua- lise and to quantify the distribution of radiopharmaeeuti- eals within the body by means of external deteetors, nuelear medieine teehniques are basieally non invasive and funetion oriented. The spatial variation of the traeer distribution in the field of view, or the ehange in distribution during a time interval are interpreted as representing speeifie phy- siologie or pathophysiologie processes. As eompared to other diagnostie imaging teehniques, the spatial resolution of seintigraphie images is rather poor, their temporal resolu- tion is good. Faetors that will therefore determine the ultimate diag- nostie value of a seintigraphie study inelude 1. The speeifieity of the labelled eompounds for the process under study, 2. The resolution in time and space of the instrumentation, and its ability of measuring quantitatively tissue aetivity eoneentrations, 3. The formulation of physiologieal or pathophysiologieal models from whieh the distribution of the traeer ean be predieted. 2 While interpreting nuclear medicine data, the interrelations between these factors should permanently remain under consi- deration. The generalised use of minicomputers has resulted in major advances in information processing in nuclear medicine imaging procedures. Central to this is image digitisation.

Just prior to the 1982 Annual Meeting of the European Thyroid Association in Brussels, a number of outstanding experts in the field of X-ray fluorescence gathered at the Academisch Ziekenhuis of the Free University of Brussels in a joint effort to more clearly define the actual place and value of the latest newcomer among the techniques available for the in vivo assessment of thyroid function. It is the merit of Prof. M. Jonckheer to have organised this meeting and to have made available the work presented there to a larger public in the form of this monograph. Both, the meeting and the written accounts thereof are greatly appreciated by all thyroidologists who care for properly defining the genuine value of X-Ray fluorescence in scientific research and in clinical management of thyroid disorder. Three main conclusions can be drawn from the work presented 1. X-ray fluorescence has become a safe, convenient and reliable tool for measuring intrathyroidal iodine stores in vivo with an inter-assay reproducibility estimated at roughly 10% 2. X-ray fluorescence, used by expert hands, is a highly interesting tool to follow changes of intra thyroidal iodine stores in time, subsequent e. g. to the exposure of the thyroid gland to excess iodine 3. In contrast, no definite place of X-ray fluorescence as a technique in routine assessment of thyroid disease is yet at the horizon This latter conclusion may appear somewhat disappointing.

Under an association contract linking the Co~ission of the European Communities and the Gesellschaft fUr Strahlen- und Umweltforschung mbH, a research programme on the patho- genesis of somatic radiation damage has been under way for a number of years. Experimental research on long-term radiation effects following the incorporation of bone-seeking radionuclides and an epidemiological study of the conse- quences for patients treated with 224Ra for therapeutical reasons have been among the main features of the work. The research carried out on tumor induction in the low dose range and for low dose rates is particularly important as regards assessing the radiation hazard to man. The second Symposium on the biological effects of 224Ra, held at Neuherberg, provided a welcome opportunity to take stock of what has been achieved so far and to discuss the own research efforts in an international setting. The dis- cussions focussed on two topical aspects of radiation protection. One aspect was the long-term effects of high-LET ionizing radiations on man and the quantitative data involved in risk assessment at low doses. The epidemiological studies and experimental research carried out under the association contract should provide facts and figures for an objective assessment of the radiation hazards from incorporated radio- nuclides, which is one of the fundamental and controversial problems of the nuclear energy debate.

AIMS OF THE COLOGNE-SYMPOSIUM ON RADIOLABELLED PLATELETS In 1976, M. Thakur et al (1) were the first to publish a paper concerning the in vivo thrombus detection with 111- In-labelled platelets. Previous attempts at scintigraphic thrombus localisation had been disappointing because of the unspecific binding of a number of the isotopes used, as well as the poor labelling efficiency or an insufficient low gamma-emitting property. Because of its physical characteristics (2.8 days half-life, 94% gamma emission) 111 Indium turned out to be the best isotope for platelet kinetic studies as well as for the measurement of platelet incorporation by Thrombi to be used up until now. The lipophile complexes of Ill-In (8-hydroxyquinoline, acetylacetone, tropolone) diffuse passively into the platelets without altering the function or the life span of the platelets. This advantage has let to an increase in the clinical applications of 1211-In labelled platelets. Today, radiolabelled platelets are used for thrombus detection in several different medical areas such as cardiology, nephrology. angiology or neurology. Even though many scientists and hospital doctors now routinely use radiolabelled platelet as a diagnostic tool, there is as yet not a standardized labelling method. In addition to this, there are neither standardized image procedures for the different clinical applications nor an agreement about specificity and sensitivity of the method. In 1983, a symposium on Radiolabelled Cellular Blood Elements was organized by M.Thakur, M.R.Hardeman and M.D.

This volume highlights the remarkable new developments in brain imaging, including those that apply magnetic resonance imaging (MRI) and Positron Emission Tomography (PET), that allow us to non invasively study the living human brain in health and in disease. These technological advances have allowed us to obtain new and powerful insights into the structure and function of the healthy brain as it develops across the life cycle, as well as the molecular make up of brain systems and circuits as they develop and change with age. New brain imaging technologies have also given us new insights into the causes of many common brain disorders, including ADHD, schizophrenia, depression and Alzheimer's disease, which collectively affect a large segment of the population. These new insights have major implications for understanding and treating these brain disorders, and are providing clinicians with the first ever set of biomarkers that can be used to guide diagnosis and monitor treatment effects. The advances in brain imaging over the last 20 years, summarized in this volume, represent a major advance in modern biomedical sciences. The Authors of this volume are leaders in the development of PET and MRI methods as well as clinical and translational researchers skilled in their use in patients with brain disorders. Individual chapters of this volume focus on the use of specific methodologies, covering the full range of PET chemistry based approaches as well as MRI methods from structural and diffusion tensor based imaging, to functional MRI of functional brain circuitry, to pharmacological MRI and MRI spectroscopic molecular imaging.

A compilation of researchers' experience in the areas of bioanalysis, pharmacokinetics, and drug metabolism, to present an up-to-date and comprehensive treatise on the application of these and related technologies in drug discovery, development, and clinical use. Contents cover descriptions of analytical methods, in vitro metabolism technology and membrane transport, reappraisal of classical pharmacokinetic problems, and the time course of drug action. The book concludes with a description of PET and imaging methods in pharmacokinetics and an appendix containing a critical appraisal of computer methods and pharmacokinetic software available for PCs.

Pediatric Radiology texts typically provide only a cursory discussion of pediatric nuclear medicine techniques and applications while pediatric nuclear medicine texts typically review the so-called "structural imaging" modalities in only a superficial fashion. The standard texts do not adequately address the similarities and differences among different imaging modalities (X-rays, scintigraphy, ultrasonography, angiography, CT, MRI, etc.). The result is that the reader of these texts can not gain an understanding of the true role of nuclear medicine in pediatrics. With PEDIATRIC SKELETAL SCINTIGRAPHY, DRS. Connolly and Treves demonstrate the relative merits of scinitigraphy and other imaging tests in evaluating pediatric skeletal disorders. The emphasis is on situations where a complementary relationship exists between nuclear medicine and other modalities. In addition to showing cases in which scintigraphy is abnormal and structural imaging normal, the book also features cases where both scintigraphy and structural imaging are abnormal. The reader will gain an understanding of what can be gained from each modality, and when specific studies are indicated.

The main subject of this book is the investigation of cardiac function and in particular ventricular function with radionuclide-based techniques. Emphasis is given to the study of clinical cases which can routinely occur in the life of a busy cardiological practice, by comparing conventional techniques, such as the electrocardiogram, the echocardiogram or the catheter study, with the newer nuclear medicine imaging procedures. Four basic images are given (end systole, end diastole, amplitude and phase), obtained either with a first pass or an equilibrium methodology, and the information analyzed. The clinical material is not exhaustive but covers a broad spectrum, with examples of coronary artery disease, valvular disease, cardiomyopathy, conduction disease and congenital heart disease. The book is aimed not only at the practising specialist (cardiologist, radiologist, nuclear medicine physician) but also at the general physician and surgeon interested in finding out what modern non invasive nuclear medicine procedures have to offer in the investigation of the heart. London, June 1982 ACKNOWLEDGEMENTS We are specially grateful to the Sir Jules Thorn Charitable Trust for its continuous support and interest."

This book provides a contemporary reference to the science, technology and clinical applications of PET and PET/CT. The book is designed to be used by residents and fellows training in medical imaging specialties as well as imaging experts in private or academic practice who need to become familiar with this technology and its applications. It is also for use by those whose specialties carry over to PET and PET/CT, referring physicians such as oncologists, cardiologists, neurologists and surgeons.

Developed as an offshoot/update of the "clinical practice" portion of the main book, edited by PE Valk et al, published in 2003 (Positron Emission Tomography: basic science and clinical practice), this offshoot covers the second half of the main book only, dealing with mainly the clinical research and practice. Most of the book comprises chapters updated from the "Clinical practice" portion of the main Valk book. It contains 6 brand new chapters and 22 completely revised and updated chapters from the main Valk book.

This book contains a selection of communications presented at the Third International Meeting on Fully Three-Dimensional Image Reconstruction in Radiology and Nuclear Medicine, held 4-6 July 1995 at Domaine d' Aix-Marlioz, Aix-Ies-Bains, France. This nice resort provided an inspiring environment to hold discussions and presentations on new and developing issues. Roentgen discovered X-ray radiation in 1895 and Becquerel found natural radioactivity in 1896 : a hundred years later, this conference was focused on the applications of such radiations to explore the human body. If the physics is now fully understood, 3D imaging techniques based on ionising radiations are still progressing. These techniques include 3D Radiology, 3D X-ray Computed Tomography (3D-CT), Single Photon Emission Computed Tomography (SPECT), Positron Emission Tomography (PET). Radiology is dedicated to morphological imaging, using transmitted radiations from an external X-ray source, and nuclear medicine to functional imaging, using radiations emitted from an internal radioactive tracer. In both cases, new 3D tomographic systems will tend to use 2D detectors in order to improve the radiation detection efficiency. Taking a set of 2D acquisitions around the patient, 3D acquisitions are obtained. Then, fully 3D image reconstruction algorithms are required to recover the 3D image of the body from these projection measurements.