RESUMEN
[(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.
RESUMEN
The influence of metal cations (Fe³âº, Fe²âº, In³âº, Cu²âº, Ca²âº, Al³âº, Co²âº, Lu³âº, Ni²âº, Pb²âº, Ti4âº, Y³âº, Yb³âº, Zn²âº, and Zr4âº) on the radiolabeling yield of [68Ga(DOTATATE)] was evaluated. Our most important observation was that, within our experimental limit, the metal ion/ligand ratio plays a critical role on the influence of most metal ions. More in-depth studies, with Cu²âº and Fe³âº, revealed that reaction temperature and concentration changes have little effect, but speciation changes with pH are crucial. Furthermore, we found that [68Ga(DOTATATE)] is stable in the presence of high concentrations of Fe³âº, Zn²âº and Pb²âº, but transmetalates with Cu²âº at 95°C.