Synthesis of pyridyl derivatives for the future functionalization of biomolecules labeled with the fac-[188Re(CO)3(H2O)3]+ precursor

Abstract

In this paper, we investigated three ligand systems, symmetric and asymmetric pyridyl-containing tridentate ligands (L 1 NH2 = (bis(2-pyridylmethyl)-amino)-ethylamine, L 2 H = (bis(2-pyridylmethyl)-amino)-acetic acid, L 3 NH2 = [(6-amino-hexyl)-pyridyl-2-methyl-amino]acetic acid) as bifunctional chelating agents for labeling biomolecules. These ligands reacted with the precursor fac-[ 188 Re(CO)3(H2O)3] + and yielded the radioactive complexes fac-[ 188 Re(CO)3L] (L = three ligands), which were identified by RP-HPLC. The corresponding stable rhenium tricarbonyl complexes (1–3) were allowed for macroscopic identification of the radiochemical compounds. 188 Re tricarbonyl complexes, with log Po/w values ranging from –1.36 to –0.32, were obtained with yields of ≥90% using ligand concentrations within the 10 –6 –10 –4 M range. Challenge studies with cysteine and histidine revealed the high stability properties of these radioactive complexes, and biodistribution studies in normal mice indicated a fast rate of blood clearance and high rate of total radioactivity excretion, primarily through the renal-urinary pathway. In summary, these asymmetric and symmetric pyridyl-containing tridentate ligands are potent bifunctional chelators for the future biomolecules labeling of fac[ 188 Re(CO)3(H2O)3] + .