INSTITUTE OF BIOINORGANIC AND RADIOPHARMACEUTICAL CHEMISTR~ Annual Report 1996 Cover picture: Space-filling model of a first serotonin receptor-binding technetium-99m molecule. Forschungszentrum Rossendorf e. V. Postfach 51 01 19; D-01314 Dresden Bundesrepublik Deutschland Telefon (03 51) 260 31 70 Telefax (03 51) 260 32 32 E-Mail johannsenafz-rossendorf.de FZR - I65 February 1997 AnnuaI Report 1996 Institute of Bioinorganic and Radiopharmaceutical Chemistry Editor: B. Johannsen Editorial staff: S. Seifert FOREWORD Research at the Institute of Bioinorganic and Radiopharmaceutical Chemistry of the Research Center Rossendorf Inc. is focused on radiotracers as molecular probes for diagnosis of disease. Denved from an awareness of the very important role modern nuclear medicine is playing, as expressed explicitly in the synonym in vivo biochemi~stry,this research effort has two main components: positron emission tomography (PET) technetium chemistry and radiopharmacology. To make positron emission tom~ographyavailable also in the eastern part of Germany, a PET center was established at Rossendorf. As envisaged in a contract signed in February 1995 between the Research Center Rossendorf and the Dresden University of Technology, the lnstitute is closely linked to the University Hospital in this PET center. A joint team of staff mernberc from both the lnstitute and the Department of Nuclear Medicine with the University Hospital has been working at the Rossendorf PET Center. To contribute to further exploitiation of technetium-99m with its ideal nuclear properties for single photon emission tomography (SPECT), great commitment to interdisciplinary research into technetium tracers is required. The Institute's projects therefore address new approaches to tracer design. The research activities of our Institute have been performed in three administrative1 classified groups. A PET tracer group is engaged in the chemistry and radiopharmacy of 'G and "F compounds and in the setup of the PET center, which is jointly tun by the lnstitute and the Clinic and Polyclinic of Nuclear Medicine at the University Hospital. A SPECT tracer group deals with the design, synthesis and chernical characterization of metal coordination compounds, primarily rhenium and technetium cornplexes. A biochemical group is working on SPECT and PET-relevant biochemical and biological projects. This includes the characterization and assessment of new cornpounds developed in the two synthetically oriented groups. The annual report presented here Covers the research activities of the Institute of Bioinorganic and RadiopharmaceuticalChemistry in 1996. The achievements attained so far have only been possible because of the dedication and commitment of the permanent and temporary staff, the Ph.D. students and collaborators inside and outside the Rossendorf Research Center Inc. Iwould like to extend my thanks to all of them. Bemd Johannsen CONTENTS I. RESEARCH REPORTS 1. Serotonin Receptor-Binding Technetium and Rhenium Complexes 9. Synthesis and Characterization of Ligands Derived from Partial StructureS of Ketanserin, Cisapride and MDL 72832 M. Scheunemann, H.-J. Pietzsch, H. Spies, P. Brust, B. Johannsen 2. Serotonin Receptor-Binding Technetium and Rhenium Complexe~ 10. Synthesis and Characterization of Rhenium and Technetium Complexes Derived from Partial Structures of Ketanserin, Cisapride and MDL 72832 M. Scheunemann, H.-J. Pietzsch, H. Spies, P. Brust, B. Johannsen 3. Serotonin Receptor-BindingTechnetium and Rhenium Complexes II. Affinity and Selectivity of OxorheniumOl) Complexes Derived from Ketanserin, Cisapride and MDL 72832 H.-J. Pietzsch, M. Scheunemann, P. Brust, J. Wober, H. Spies, B. Johannsen 4. Serotonin Receptor-Binding Technetium and Rhenium Complexes 12. Structural Modification of Receptor-BindingTechnetium-99m Complexes in oder to lmprove Brain Uptake B. Johannsen, R. Berger, P. Brust, H.-J. Pietzsch, M. Scheunemann, S. Seifert, H. Spies, R. Syhre 5. Serotonin Receptor-Binding Technetium and Rhenium Complexes 13. No Carrier Added Preparations of "3+lu""'TC Complexes S. Seifert, H.-J. Pietzsch, M. Scheunemann, H. Spies, R. Syhre, B. Johannsen 6. Serotonin Receptor-Binding Technetium and Rhenium Complexes 23 14. Distribution and Brain Uptake in Rats of Serotonin Receptor-Binding Oxotechnetium01) Complexes at the c.a. (99m9 Tc) and the n.c.a. (99m~c)Level R. Syhre, H.-J. Pietzsch, M. Scheunemann, S. Seifert, H. Spies. B. Johannsen 7, Serotonin Receptor-Binding Technetium and Rhenium Complexes 15. Synthesis and Characterization of Oxorhenium01) Complexes with N-Functionalized Tridentate SWS Ligands H.-J. Pietzsch, M. Scheunemann, R. Berger, H. Spies, B. Johannsen 8. Synthesis of Neutral Amine Groiup Bearing "3+IuMixed-Ligand Complexes of 35 Oxorhenium01) M. Friebe, M.Papadopoulos, S.Chiotellis, H. Spies, R. Berger, B. Johannsen 9. Preparation of Amine Group Bearing "3+IuMixed-Ligand Oxotechnetium01) 40 complexes at the camer added level M. Friebe, M.Papadopoulos, E.Chiotellis, H. Spies, R. Berger, B. Johannsen 10. Lipophilicity and lonization Properties of Some Amine-Bearing Technetium and 43 Rhenium "3+lUMixed-Ligand Chelates with Same Ligand Structure R. Berger, M. Friebe, H.-J. Pietzsch, M. Scheunemann, B. Noll, T. Fietz, H. Spies, B. Johannsen 11. Retropane - a New Rhenium Complex as a Potential Ligand of the Dopamine Transporter A. Hoepping, H. Spies, B. Johannsen 12. Preparation and Structure of Neutral 0x0-Re01)-Complexes with L-Cysteine Methyl Ester and D-Peniciliamine Methyl Ester S. Kirsch, B. Noll, H. Spies, B. Johannsen, P. Leibnitz, D. Scheller 13. Formation of Mixed-Ligand Ester Complexes of Rhenium and Technetium with S/S/S-N or S-S/S-N Coordination S. Seifert, H. Spies 14. A Novel Amide Thioether Dithiolate Ligand Derived from Cysteine B. Noll, S. C. Hilger, P. Leibnitz, H. Spies, L. Dinkelborg, B. Johannsen 15. Novel OxorheniumO/) Complexes with Cysteinylglycine and Glycylglycylcysteine: Preparation and Characterization in Solution S. Kirsch, R. Jankowsky, B. Noll, H. Spies, B. Johannsen, D. Scheller 16. Synthesis and Characterization of Technetium and Rhenium Oligoglycine Complexes and Technetium Tartrate R. Jankowsky, B. Nol, H. Spies, B. Johannsen 17. XAS Investigations on Tc and Re Complexes of Oligoglycine Ligands and Tc Tartrate R. Jankowsky, B. Noll, H. Spies, B. Johannsen 18. X-Ray Absorption Spectroscopy: A Valuable Tool for Structural Analysis of Tc and Re Complexes R. Jankowsky, B. Noll, H. Spies, T. Reich, H. Nitsche 19. Technetium and Rhenium Complexes with Thioether Ligands. 8. X-Ray Structures of Mononuclear Oxorhenium01) Complexes with Bidentate Thioether and Dithiaalcohol Ligands M. Reisgys, H.-J. Pietzsch, H. Spies, P. Leibnitz 20. Rhenium and Technetium Carbonyl Complexes for the Labelling of Bioactive Molecules. 2. Tricarbonylrhenium(1) Complexes with Mono-, Bi- and Tridentate Thioether Ligands H.-J. Pietzsch, M. Reisgys, H. Spies, R. Albedo, U. Abram 21. Technetium and Rhenium Labelled Steroids. I.First Synthesis of "3+lVMixed-Ligand Oxorhenium01) Complexes Bearing a Pendent Estradiol Moiety F. Wüst, H. Spies, D. Scheller, S. Machill 22. Technetium and Rhenium Labelled Steroids. 2. Oxorhenium01) Complexes of 1-Mercapto-4-Methylestra-I ,3,5(10)-trien-I 7-one F. Wüst, H. Spies, R. Becked, S. Möller 23. Structure and Reactivity of a "3+IuMixed-Ligand Rhenium Complex Containing Thiobenzoate as a Monodentate Ligand [ReO(SSS)(SC(O)Ph)J B, Noll, P. Leibnitz, St. Noll, R. M. Mahfouz, H. Spies 24. Nicotinamide Substituted Rhenium0 Mixed-Ligand Complexes T. Kniess, H. Spies 25. Dihydropyiidine Substituted TechnetiurnOl) Mixed-Ligand Complexes T. Kniess, H. Spies 26. Note to Fast Hydrolysis of the Methyl Ester of MAGz during Complexation with TcJRe(V) Gluconate St. Noli, B. Noll, H. Spies 27. Synthesis of la6~eGluconate by Stannous Chloride Reduction of lE6~e0i B. Noll, T. Kniess, H. Spies 28. Determination of Partition Coefficients for Coordination Compounds by Using the HPLC Column Nucleogel RP Cla 80-10 R. Berger, T. Fietz, M. Glaser, H. Spies 29. lnvestigations of Serotonin Receptor Subtypes on the Blood-Brain Barrier J. Wober, S. Matys, P. Brust 30. Comparison of a Microplate Assay with Conventional Binding Assay for the Screening of Potential Receptor Ligands J. Wober, P. Brust 31. Functional Expression of P-Glycoprotein in an lmmortalized Rat Brain Endothelial Cell Line (RBE4) in vitro R. Bergmann, S. Matys, P. Brust 32. Different Response of Cerebral and Non Cerebral Endothelial Cells to Cytotoxic Hypoxia. B. Ahlemeyer, P. Brust, B. Johannsen 33. Studies on an HPLC Method to Assay the Concentrations of Amines in Brain Micro- dialysis Perfusates Based on Naphthalene-2,3-Dicarbaldehyde Derivatization and Fluorescence Detection G. Vorwieger, R. Bergmann, P. Brust, B. Johannsen 34. High-Affinity Binding of [3~]~aroxetineto Caudate Nucleus and Microvessels from Porcine Brain P. Brust, R. Bergmann, B. Johannsen 35. Measurement of the Cerebral Uptake and Metabolism of L-6-["~] Fluoro-3,4-Dihydroxy-Phenylalanine in Newborn Piglets P. Brust, R. Bauer, R. Bergmann, B. Walter, J. Steinbach, F. Füchtner, E. Will, H. Linemann, M. Obert, U. Zwiener, B. Johannsen 36. High Yield Preparation of 6-['8~]~luoro-~~~~ F. Füchtner, K. Günther, J. Steinbach, R. Lücke, R. Scholz, R. Hüller 37. Modified Access to the Thioester Precursor of ["C](+)-MCN-5652-z J. Zessin, P. Brust, J. Steinbach 38. Substances Labelled in Metabolically Stable Positions: The Conversion of Pyrylium Salts with Nitro-["clmethane - a New Method for the Synthesis of n.c.a.