I.: A novel tetraazamacrocycle bearing a thiol pendant arm for labeling biomolecules with radiolanthanides. Dalton Trans

Abstract

The novel tetraazamacrocycle 10-(2-sulfanylethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (H 4 DO3ASH) was synthesized and characterized by multinuclear NMR spectroscopy, 2D NMR techniques and mass spectrometry. The protonation constants of H 4 DO3ASH were determined by potentiometry at 25 • C in 0.1 M KCl ionic strength, and the protonation sequence was assigned based 153 Sm, logD = -2.1; 166 Ho, logD = -1.6) has been studied in different buffers, in human serum and in the presence of excess of cysteine and glutathione. 153 Sm-DO3ASH has shown a high stability under these conditions and a relatively low protein binding (2.1%), while 166 Ho-DO3ASH was less stable, including in the presence of cysteine and glutathione, and had a slightly higher protein binding (6.7%). In vivo studies have been performed only for the more stable 153 Sm-DO3ASH complex and its biological profile and in vivo stability has been compared to that of 153 Sm-DO3A in the same animal model. The biodistribution profile presents a similar trend with rapid total excretion from the whole animal body, mainly via the urinary pathway. The most striking difference found is related to a slightly slower clearance of 153 Sm-DO3ASH from organs like blood, bone and muscle as compared to 153 Sm-DO3A. Additionally, the fraction of 153 Sm-DO3ASH taken by the hepatobiliar tract is also modestly higher than that of 153 Sm-DO3A