Binding of technetium-99m to plasma proteins: influence on the distribution of Tc-99m phosphate agents

Plasma protein binding of Tc-99m was assessed in man after injection of various Tc-99m-labeled bone imaging agents. Of the five methods in which plasma proteins were precipitated to determine protein binding no correlation between them could be established. The ammonium sulfate method seemed to correlate well with dialysis filtration. Plasma obtained from patients injected with Tc-99m phosphate compounds was reinjected to rats. The bone uptake in these animals correlated linearly with the unbound activity in the injected plasma. Provided that no protein binding would occur, the bone uptake as well as the urinary excretion proved to be identical for Tc-99m HEDP, MDP, and PPi. Electrophoresis of Tc-99m PPi indicated that the intact complex may be uncharged, whereas at low ligand concentrations uncharged as well as negatively charged Tc-99m species are formed. Better methods are needed, however, to establish the presence of various Tc-99m species and their relative role in the kinetics of these compounds, and plasma protein binding.