Preparation and characterization of technetium and rhenium tricarbonyl complexes bearing the 4-nitrobenzyl moiety as potential bioreductive diagnostic radiopharmaceuticals. In vitro and in vivo studies.

The synthesis of a ligand containing a nitrobenzyl group as bioreductive pharmacophore and the preparation of the corresponding technetium and rhenium complexes are presented. (99m)Tc labelling was performed in high yield (>90%) by ligand substitution using fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) as precursor. The structure of the technetium complex was established by chromatographic comparison with the analogous rhenium compound which was fully characterized by elemental analysis, spectroscopic methods and X-ray crystallography. Reduction potential of the rhenium complex was in the characteristic range for bioreductive compounds. Biodistribution in normal mice was characterized by fast blood and soft tissue depuration and combined excretion via the hepatobiliary and urinary systems. Tumour uptake was low, probably due to low lipophilicity but tumour/muscle ratios were favourable as a consequence of high excretion.