Influence of cations on the complexation yield of DOTATATE with yttrium and lutetium: a perspective study for enhancing the 90Y and 177Lu labeling conditions

The DOTA macrocyclic ligand can form stable complexes with many cations besides yttrium and lutetium. For this reason, the presence of competing cationic metals in yttrium-90 and lutetium-177 chloride solutions can dramatically influence the radiolabeling yield. The aim of this study was to evaluate the coordination yield of yttrium- and lutetium-DOTATATE complexes when the reaction is performed in the presence of varying amounts of competing cationic impurities. In the first set of experiments, the preparation of the samples was performed by using natural yttrium and lutetium (20.4 nmol). The molar ratio between DOTATATE and these metals was 1 to 1. Metal competitors (Pb2+, Zn2+, Cu2+, Fe3+, Al3+, Ni2+, Co2+, Cr3+) were added separately to obtain samples with varying molar ratio with respect to yttrium or lutetium (0.1, 0.5, 1, 2 and 10). The final solutions were analyzed through ultra high-performance liquid chromatography with an UV detector. In the second set of experiments, an amount of 90Y or 177Lu chloride (6 MBq corresponding to 3.3 and 45 pmol, respectively) was added to the samples, and a radio-thin layer chromatography analysis was carried out. The coordination of Y3+ and Lu3+ was dramatically influenced by low levels of Zn2+, Cu2+ and Co2+. Pb2+ and Ni2+ were also shown to be strong competitors at higher concentrations. Fe3+ was expected to be a strong competitor, but the effect on the incorporation was only partly dependent on its concentration. Al3+ and Cr3+ did not compete with Y3+ and Lu3+ in the formation of DOTATATE complexes.