Untersuchungen zur Synthese, Charakterisierung und Bioverteilung von Komplexen des Technetiums ($^{99}$Tc/$^{99}$Tc) mit 2-Amino-2-deoxy-D-hexoseoximen)

In view of the diverse potential applications of technetium complexes in nuclear medicine diagnostics, it is of interest to produce such complexes which behave similarly to D-hexoses in the organism. According to the current state-of-the-art, it has not yet proved possible to complex technetium in weighable quantities with hexoses or their derivatives and to determine the bio-distribution of the characteristic complexes in the organism. In the present work, the synthesis and isolation ofisomeric complexes of technetium ($^{99}$ Tc/ $^{99m}$Tc) with the 2-amino-2-deoxy-D-hexoses D-glucose aminoxime, D-galactose aminoxime and D-mannose aminoxime, the characterization of the complexes as $^{99}$Tc compounds, and bio-distribution studies on the analogous $^{99}$Tc complexes have been undertaken. As a first step, the free ligands were synthesized and identified using elemental analysis, infra-red and nuclear magnetic resonance spectroscopy and FAB mass spectroscopy. The $^{99}$Tc complexes were produced by reduction of ammonium pertechnetate using sodium dithionite in a neutral aqueous solution of the 2-amino-2-deoxy-D-hexose oxime. Finally the reaction products were purified using ion exchange, solvent extraction and precipitation. As end product, a light brown powder was obtained which was stable in air. The purity of the powder was investigated using high-performance liquid chromatography (HPLC). Because a successful HPLC separation of transition metal complexes with carbohydrates or their derivatives has not been described up to now, an HPLC technique was developed to analyse and separate the technetium complexes under investigation. The separation system used silica gel as stationary phase with chemically bound vic-hydroxyl groups combined with an acetonewater mixture as eluant. The isomeric $^{99}$Tc complexes selected by analogy considerations based on the chromatograms could be separated using HPLC. These complexes are to the author's knowledge the first carbohydrate-containing, water stable technetium complexes that have been investigated in pure form. The brown, X-ray amorphous substances were shown by electrophoretic investigations to be cationic and based on their solubility behaviour extremely hydrophylic. The composition of the $^{99}$Tc complexes was determined using C, H and N elemental analysis, anionchromatography and $\beta^{-}$ scintillation measurements. In addition, the complexes were examined by IR/UV/VIS spectroscopy, $^{1}$H/$^{13}$C nuclear resonance spectroscopy and FAB or FD mass spectroscopy. The analytical data indicated that the complexes each contained, as single nucleus compounds, three ligands coordinated by the 2-amino-l-oxime group, which were connected to each other by two intramolecular hydrogen bridges. The Tc central atom was probably in the +3 oxidation state