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I. E. Markó [Université catholique de Louvain, Belgium]—Novel Orthoesters in Organic Synthesis.S. J. Harwood [GlaxoSmithKline, UK]—The Synthesis of Stable Labelled Ketamine.Th. Moenius, R. Salter, B. Wietfeld, P. Burtscher, C. Zueger [Novartis, Switzerland]—C‐13, C‐14, N‐15 Labelling of the 4‐Cyanobenzyl bromide – A Versatile Labelling Building Block.J. Clayden [University of Manchester, UK]—Synthesis and Stereocontrol with Lithiated Amides.R. Salter, K. Bordeaux, P. Burtscher, Y. Metz, Th. Moenius, I. Rodriguez, R. Ruetsch, R. Voges, C. Zueger [Novartis, Switzerland]—Isotopic Labelling of STI571 and its Metabolites in the Development of Gleevec®.J. M. Gardiner, W. Stimpson, N. Panchal [University of Manchester, UK], J. Herbert, G. J. Ellames [Sanofi‐Aventis, UK]—Synthesis of Labelled Carbohydrates.M. Beller [Rostock University, Germany]—Homogeneous Catalysis – A Powerful Tool for the Synthesis of Pharmaceuticals.J. Kozempel, J. Kadeřávek, L. Lešetický, O. Lebeda [University of Prague, Czech]—Preparation of Ortho‐radiohalogenated Phenylazides and Triazenes, Versatile Building Blocks for Indirect Labelling.K. Wähälä, P. Kiuru, E. Leppälä, M. Pohjoispää, K. Parikka, B. Raffaelli [University of Helsinki, Finland]—Controlled Polydeuteration of Estrogenic Compounds.J. M. Herbert [Sanofi‐Aventis, UK]—Catalyst Stability in Iridium‐mediated Isotope Exchange.C. G. M. Janssen, W.L.M. Verluyten, M. Vliegen [Johnson & Johnson Pharmaceutical, Belgium]—Pd/C Catalysed Hydrogenolytic H/T Exchange in Solvents, Effects on Solvents and Product in a Bromine‐tritium Exchange Reaction.P. Mäding, F. Füchtner, R. Bergmann, J. Pietzsch, C. Hultsch, F. Wüst [Forschungszentrum Rossendorf, Germany]—A New Module‐Assisted Synthesis of the Versatile, Bifunctional Labelling Agent [18F]SFB: From Radiochemistry to Applications.M. Scheunemann, J. Vercouillie, St. Fischer, J. Steinbach [Institut für Interdisziplinäre Isotopenforschung Leipzig, Germany], D. Sorger, U. Großmann, O. Sabri, R. Schliebs [University Leipzig, Germany]—Syntheses and First Biological Evaluation of 18F Labelled Bicyclic Analogues of Vesamicol as Potential VAChT Imaging Agents.

Summary.: The human organism is exposed to numerous processes that generate reactive oxygen species (ROS). ROS may directly or indirectly cause oxidative modification and damage of proteins. Protein oxidation is regarded as a crucial event in the pathogenesis of various diseases ranging from rheumatoid arthritis to Alzheimer’s disease and atherosclerosis. As a representative example, oxidation of low density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Data concerning the role of circulating oxidized LDL (oxLDL) in the development and outcome of diseases are scarce. One reason for this is the shortage of methods for direct assessment of the metabolic fate of circulating oxLDL in vivo. We present an improved methodology based on the radiolabelling of apoB-100 of native LDL (nLDL) and oxLDL, respectively, with the positron emitter fluorine-18 (18F) by conjugation with N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). Radiolabelling of both nLDL and oxLDL using [18F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively, in vitro. The method was further evaluated with respect to the radiopharmacological properties of both [18F]fluorobenzoylated nLDL and oxLDL by biodistribution studies in male Wistar rats. The metabolic fate of [18F]fluorobenzoylated nLDL and oxLDL in rats in vivo was further delineated by dynamic positron emission tomography (PET) using a dedicated small animal tomograph (spatial resolution of 2 mm). From this study we conclude that the use of [18F]FB-labelled LDL particles is an attractive alternative to, e.g., LDL iodination methods, and is of value to characterize and to discriminate the kinetics and the metabolic fate of nLDL and oxLDL in small animals in vivo.

Summary.: Isopeptide bonds between the ɛ-amino group of lysine and the γ-carboxamide group of glutamine are formed during strong heating of pure proteins or, more important, by enzymatic reaction mediated by transglutaminases. Despite the wide use of a microbial transglutaminase in food biotechnology, up to now little is known about the metabolic fate of the isopeptide Nɛ-(γ-glutamyl)-L-lysine. In the present study, N-succinimidyl-4-[18F]fluorobenzoate was used to modify Nɛ-(γ-glutamyl)-L-lysine at each of its two α-amino groups, resulting in the 4-[18F]fluorobenzoylated derivatives, for which biodistribution, catabolism, and elimination were investigated in male Wistar rats. A significant different biochemical behavior of the two labelled isopeptides was observed in terms of in vitro stability, in vivo metabolism as well as biodistribution. The results suggest that the metabolic fate of isopeptides is likely to be dependent on how they are reabsorbed – free or peptide bound.