Amine group bearing '3+1' oxotechnetium(V) and oxorhenium(V) complexes: Synthesis, characterization of lipophilicity and permeation through the blood-brain barrier

A set of technetium(V) mixed-ligand complexes was synthesized with different protonation constants pK_a, brought about by substitution. They were characterized regarding their lipophilicity and compared to the corresponding rhenium(V) complexes. Partition coefficients P, determined by reversed phase HPLC and the octanol shake flask method, were higher for the technetium than for the analogous rhenium species. Investigations were performed to assess the influence of the physicochemical molecule parameters on the biological behaviour of these compounds. The state of ionisation of the molecules had a significant influence on brain uptake in vivo. Less uptake was found for compounds with pK_a values around 9.5, which are fully protonated at physiological pH, than for those with pK_a values around 7.5, which are ionised to only about 50% at pH 7.4. transport through cells was studied with an in vitro blood-brain barrier (BBB) model, based on the human umbilical cord cell line ECV304. The resulting in vitro permeation curves agree with the in vivo results obtained in mice and rats with short incubation times (up to 30 min).