Compounds which mediate gallium-67 transfer from lactoferrin to ferritin.

The influence of various low molecular weight compounds on the transfer of 67Ga from human lactoferrin (LF) to horse spleen ferritin (HoFE) has been examined in vitro. When LF67Ga complex was placed in competition with HoFE using a dialysis system the initial transfer rate (TR) of 67Ga to HoFE was slow and continuous. In the presence of 1 mM pyrophosphate (PPi) ascorbate and adenosine triphosphate (ATP), the TR was dramatically enhanced. This effect was concentration sensitive since reduction of the ATP to 0.1 mM eliminated the enhancement. Other intracellular compounds did not significantly influence the TR. Although PPi and ascorbate ions yielded larger TR's, ATP was more effective in the promotion of 67Ga transfer to HoFE. When the LF/HoFE concentration ratio was decreased, in the presence of ATP, the transfer of 67Ga was significantly increased. These results suggest that ferritin present intracellularly could remove and retain 67Ga entering the cell in the form of a LF67Ga complex. Moreover, increased synthesis of ferritin and cytosolic phosphate compounds would appear to enhance this process.