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.

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.

During the last two decades significant advances have been made in the in vivo-diagnosis of gastrointestinal diseases. Although Ultrasound and CT as well as Endoscopy have had a major impact on the evaluation of liver, pancreas and bile diseases, there are a lot of indications for Nuclear Medicine procedures. These include new investigational procedures like esophageal scintigraphy, proof of bleeding sites, scintigraphy of inflammatory diseases, and intestinal resorption tests. Further, immunoscintigraphy with radiol- elled antibodies has gained wide-spread application especially in colon cancer. The differential diagnosis of liver tumors like haemangioma and focal nodular hyperplasia by means of blood pool and HID A-scintigraphy is nowadays a routine procedure. Other established methods like hepatobiliary scintigraphy and liver perfusion scintigraphy have proved to be reliable tools in the pre-and postoperative evaluation of patients with bile duct obstruction and portal hypertension. The aim of this book is to present the entire spectrum of Nuclear Medicine in Gastroenterology to our colleagues from internal medicine and surgery. Ultrasound and Sonography as well as CT will rule the field of gastroenterology, but there remain a certain number of unanswered questions. Nuclear Medicine provides a lot of reliable answers. H. J. Biersack and P. H. Cox July 1990 VB List of contributors Duncan M. Ackery, Department of Nuclear Medicine, Southampton General Hospital, Tremona Road, Southampton, Hampshire S09 4XY, U. K. Roland Bares (co-author: U. Buell), Department of Nuclear Medicine, Te- nical University of Aachen, Pauwelsstr. 1, DW-5100 Aachen, Germany.

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. "

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.

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."

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.

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."

Despite 50 years of antibiotics, infection remains a major source of both morbidity and mortality. Immunosuppression, either secondary to drugs in transplant recipients or secondary to HIV, has expanded the number of microorganisms that are known to be pathogenic in man. Imaging of infection has a vital role both in the initial diagnosis and in the continuing management of patients with infection or suspected infection. Functional imaging using nuclear medicine techniques has a unique role to play in identifying sites of infection in a wide range of patients with varying clinical conditions. This book, written by a series of experts not just in the fields of nuclear medicine but also infectious disease and radiology, discusses the role of nuclear medicine in three parts: a review of the pathophysiology of infection; a technical description of those nuclear medicine techniques which can be used in imaging infection; an extensive systematic review including thoracic, abdominal and orthopaedic infection as well as a special section on the acutely ill patient, the immunosuppressed patient and the patient with pyrexia of unknown origin. This book will be of interest to all clinicians looking after patients with infection and who need to use imaging techniques. It will also be of use to radiologists and nuclear medicine physicians who will be using these techniques clinically.

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.

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."

Despite 50 years of antibiotics, infection remains a major source of both morbidity and mortality. Immunosuppression, either secondary to drugs in transplant recipients or secondary to HIV, has expanded the number of microorganisms that are known to be pathogenic in man. Imaging of infection has a vital role both in the initial diagnosis and in the continuing management of patients with infection or suspected infection. Functional imaging using nuclear medicine techniques has a unique role to play in identifying sites of infection in a wide range of patients with varying clinical conditions. This book, written by a series of experts not just in the fields of nuclear medicine but also infectious disease and radiology, discusses the role of nuclear medicine in three parts: a review of the pathophysiology of infection; a technical description of those nuclear medicine techniques which can be used in imaging infection; an extensive systematic review including thoracic, abdominal and orthopaedic infection as well as a special section on the acutely ill patient, the immunosuppressed patient and the patient with pyrexia of unknown origin. This book will be of interest to all clinicians looking after patients with infection and who need to use imaging techniques. It will also be of use to radiologists and nuclear medicine physicians who will be using these techniques clinically.

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) 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.

ONE: Liver and Bile.- 1 Liver scintigraphy.- 2 Differential diagnosis of jaundice with hepatobiliary scintigraphy.- 3 Kinetics of gallbladder emptying.- 4 Hepatobiliary imaging after gastrointestinal surgery.- 5 Measurements of liver haemodynamics.- 6 Hepatic scintigraphy for evaluation of liver grafts.- 7 Differential diagnosis of liver tumors.- 8 Intra-arterial liver scintigraphy with99mTc-MAA.- TWO: Stomach and Intestines.- 9 Detection of gastroduodenal ulcers using Technetium-99m-labelled sucralfate.- 10 Gastroesophageal and biliary reflux.- 11 Nuclear medicine in inflammatory bowel diseases.- 12 Detection and localization of gastrointestinal bleeding sites with scintigraphic techniques.- 13 Intestinal absorption tests.- THREE: Miscellaneous.- 14 Investigations of disorders of motility of the esophagus in chronic diseases.- 15 Radioimmunoscintigraphy in gastroenterology.- 16 Scintigraphic procedures for the proof of peritoneo-venous shunt patency.