A novel tetraazamacrocycle bearing a thiol pendant arm for labeling biomolecules with radiolanthanides
Abstract
The novel tetraazamacrocycle H3DO3ASH was synthesized and characterized by multinuclear NMR spectroscopy. The protonation constants were determined by potentiometry and the protonation sequence was assigned based on 1H and 13C-NMR titrations.
The stability constants of the DO3ASH complexes with Ce3+, Sm3+ and Ho3+ have been determined by potentiometry and UV-Vis spectroscopy. For labeling with radioactive lanthanides, various conditions were tested and both complexes, 153Sm/166Ho-DO3ASH were obtained in quantitative yield.
At room temperature, the formation kinetics have been found faster for the 153Sm than for the 166Ho complex. The stability of these complexes has been studied in different buffers, in human serum and in the presence of excess of cysteine and glutathione.
In vivo studies have been performed only for the more stable 153Sm-DO3ASH complex. The biodistribution profile presents a rapid total excretion from the whole animal body, mainly via the urinary pathway.