The role of additives in moderating the influence of Fe(III) and Cu(II) on the radiochemical yield of [68Ga(DOTATATE)]

•Additives reduce the negative effect of metal ions on the RC yield of [68GaDOTATATE].•Addition of phosphate results in excellent RC yields for a Fe3+/ligand ratio of 2:1.•Ascorbic acid was more effective with high RC yields for both Fe3+ and Cu2+.•The effect of ascorbic acid is highly pH-dependant with optimal results at pH3.

[68Ga(DOTATATE)] has demonstrated its clinical usefulness. Both Fe3+ and Cu2+, potential contaminants in Gallium-68 generator eluent, substantially reduce the radiochemical (RC) yield of [68Ga(DOTATATE)] if the metal/ligand ratio of 1:1 is exceeded. A variety of compounds were examined for their potential ability to reduce this effect. Most had no effect on RC yield. However, addition of phosphate diminished the influence of Fe3+ by likely forming an insoluble iron salt. Addition of ascorbic acid reduced Cu2+ and Fe3+ to Cu+ and Fe2+ respectively, both of which have limited impact on RC yields. At low ligand amounts (5 nmol DOTATATE), the addition of 30 nmol phosphate (0.19 mM) increased the tolerance of Fe3+ from 4 nmol to 10 nmol (0.06 mM), while the addition of ascorbic acid allowed high RC yields (>95%) in the presence of 40 nmol Fe3+ (0.25 mM) and 100 nmol Cu2+ (0.63 mM). The effect of ascorbic acid was highly pH-dependant, and gave optimal results at pH 3.