¹⁸⁸Re(III)-„4+1“-Mixed-ligand Complexes: Stability Studies and Labeling of Biomolecules

In oder 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 and determined their stability in human plasma. Rhenium-188 '4+1' complexes were synthesized using different monodentate phosphorus(III) ligands, including both lipophilic and hydrophilic tertiary phosphines and phosphites (188Re1-3) and unsubstituted tetradentate ligands and substituted NS3 ligands bearing a carboxyl group or an isopropyl amide were used as chelators (188Re4-6). As instability in aqueous solution leads always to perrhenate, the amount of 188ReO4- formed after 1h, 24 h and 48 h was determined by TLC. According to our findings 188Re4 was of sufficient stability and therefore used for further investigations. We tried to find out which physico-chemical parameter of the corresponding non-radioactive rhenium complexes Re1-6 may govern the formation of complexes of high in vitro stability. The water-soluble N-hydroxysulfosuccinimidyl activated ester 1 is a useful compound for the conjugation of exclusively water soluble biomolecules. Rhenium-188 labeling of the phosphine-arginine-tyrosine conjugate 2 as model compound was carried out using a labile 188Re(III)-EDTA intermediate. Based on this procedure peptides and proteins shall by labeld and tested in vivo.