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

Abstract

[(68)Ga(DOTATATE)] has demonstrated its clinical usefulness. Both Fe(3+) and Cu(2+), potential contaminants in Gallium-68 generator eluent, substantially reduce the radiochemical (RC) yield of [(68)Ga(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 Fe(3+) by likely forming an insoluble iron salt. Addition of ascorbic acid reduced Cu(2+) and Fe(3+) to Cu(+) and Fe(2+) 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 Fe(3+) 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 Fe(3+) (0.25 mM) and 100 nmol Cu(2+) (0.63 mM). The effect of ascorbic acid was highly pH-dependant, and gave optimal results at pH 3.

Keywords: (68)Ga radiolabelling; Additives; Ascorbic acid; DOTATATE; Metal ion contamination; PET.; Phosphate.