Bøger i Developments in Nuclear Medici serien

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.

"More than half of the world's population is at risk of the tropical diseases malaria, leprosy, schistosomiasis, lymphatic filariasis, onchocerciasis, Chagas' disease, African trypanosomiasis and leishmaniasis and half a billion are infected with at least one of these diseases". J. H. F. Remme, World Health Organisation, 1993. "If it is true that science is not limited by frontiers and all research Institutions then belong to mankind, so it is natural for each Institution to be responsible for the problems of those who live in the geographic area under its influence. There are no specific aspects concerning physical, chemical or philosophical concepts and facts, but specificity does exist concerning geology, sociology and pathology. It is the duty of each Institution to study the particular aspects concerning its geographic region, as missing links of the chain of universal knowledge may be found there." H. L. de Oliveira, fonner Rector of the University ofSiio Paulo, 1967. "Nuclear Medicine is cost effective, especially in the developing countries. ( ... ).

I. Riblets.- Experiments with a 1:4.2 model of a commuter aircraft with riblets in a large wind tunnel.- Heat transfer study of riblets.- Performances of internal manipulators in subsonic three-dimensional Flows.- High resolution conformal mesh computations for V, U or L groove riblets in laminar and turbulent boundary layers.- Coherent structures over a smooth and a triangular riblet drag reducing surface.- Some further experiments on riblet surfaces in a towing tank.- II. LEBUs.- Analytical and experimental study of energy density spectra of the outer region of a manipulated turbulent boundary layer.- Review: effect of the OLDs on near wall coherent structures; discussion and need for future work.- III. Surface Roughness.- Turbulent drag reduction of a d-type rough wall boundary layer with longitudinal thin ribs placed within the traverse grooves.- The correlation of added drag with surface roughness parameters.- IV. Compliant Surfaces.- The optimisation of compliant walls for drag reduction.- Nonlinear evolution of modes in the flow over compliant surfaces.- On conditions of modelling and choice of viscoelastic coatings for drag reduction.- Experimental investigation of one-layer viscoelastic coatings action on turbulent friction and wall pressure pulsations.- V. Polymer Additives.- The pulseless injection of polymeric additives into near-wall flow and perspectives of drag reduction.- Initial section of time-dependence of the Toms effect for solutions of poly (ethylene oxide).- Panel discussions.- List of Referees.- List of Participants.- Author Index.

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.

Safety and efficacy of radiopharmaceuticals are elements of great importance in nuclear medicine. Since the first meeting in 1965 in Oak Ridge with the title Radiopharmaceuticals tremendous developments have taken place. In 1965 the whole technetium-99m area was just in its very beginning. Safety and efficacy of the non-radioactive pharmaceuticals have attracted great attention during the last 10 years and so have similar aspects of radiopharmaceuticals during the later years. Regulatory agencies are extending their work also to the preparation of radiopharmaceuticals at hospitals and to requirements for registration of radiopharmaceuticals. In a fast developing field there might be tendencies to confrontation between interests and there have certainly been some tendencies to put undue restrictions on the use of radio­ pharmaceuticals due to the lack of understanding between the industry and the regulatory authorities and between regulatory authorities and hospitals. Much of this may have been due to lack of information and certainly is due to the lack of fundamental scientific knowledge in many radiopharmaceutical aspects. A fast and safe introduction of new radio­ pharmaceuticals and the proper handling of these requires a lot of development work, but also an understanding of how general principles from the non-radioactive drug field may be sensibly transformed into the radiopharmaceutical area. It may even require compromises between requirements for safety in different areas such as radiation protection and pharmaceutical aspects.

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.