188Re(III) Mixed-ligand Complexes: Stability Studies and Labeling of Biomolecules

Trigonal-bipyramidal Re(III) complexes with tetra-dentate/monodetate NS3/P ‘4+1’-coordination are inter-esting agents for the development of rhenium-188 com-plexes for potential therapeutic application. In order to understand relationships between the structure of rhenium-188 ‘4+1’ complexes and their in vitro stability we synthesized a series of rhenium model complexes 1, 2 and determined their stability in human plasma.
The complexes were prepared as described in [1] using various combinations of NS3 derivatives and mono-dentate phosphorus(III) ligands.
Since instability in aqueous solution always leads to the formation of perrhenate, we determined the amount of perrhenate formed after 1h, 24 h and 48 by TLC.
By means of physico-chemical parameters of the corres-ponding non-radioactive rhenium complexes we tried to find factors which may govern the formation of complexes showing high in vitro stability.
Finally, the most stable representative 3 was studied in 188Re labeling experiments with a phosphine-arginine-tyrosine model conjugate using the water-soluble N-hydroxysulfosuccinimidyl ester of the monodentate phosphine.