Decorporation
therapy is the only known effective method of reducing the radiation dose to persons following accidental internal contamination with transportable
radionuclides. Deposits of
actinides in bone should be minimized because development of
osteosarcoma appears to be related to internal exposure. In contrast with other
actinides, such as
plutonium or
americium where
chelating agent treatment is efficient, the therapeuric approaches used for cases of
uranium contamination are widely ineffective. This is the first report on in vivo efficacy of a
chelating agent, a
siderophore analogue code named
3,4,3-LIHOPO, after systematic exposure to natural
uranium in the rat. Using the classical antidotal
therapy (
sodium bicarbonate) for comparison, this
ligand has been investigated for its ability to remove
uranium from rats after intravenous or
intramuscular injection as
nitrate. Following an immediate single intramuscular or
intravenous injection of
3,4,3-LIHOPO (30 mumol.kg-1) urinary excretion of
uranium was greatly enhanced with a corresponding reduction 24 h later in kidney and bone
uranium content (to about 20 and 50% of the control rat respectively). Under identical experimental conditions,
sodium bicarbonate (640 mumol.kg-1) reduced the
uranium content in kidney in kidney and bone only to about 90 and 70% of controls respectively, and there was less enhancement of
uranium excretion. However, when treatment was delayed by 30 min and administered intraperitoneally, there was no marked difference in retention and excretion of
uranium between the two compounds. As this
ligand showed no apparent irreversible toxicity at effective dosages, it is concluded that the administration of the
3,4,3-LIHOPO chelating agent represents potentially a most significant advance for prompt treatment of
uranium contamination, while a more detailed investigation is necessary on the possible advantage when
treatment delayed.