EFFICACY OF 3,4,3-LIHOPO FOR REDUCING THE RETENTION OF URANIUM IN RATAFTER ACUTE ADMINISTRATION

Decorporation therapy is the only known effective method of reducing t he radiation dose to persons following accidental internal contaminati on with transportable radionuclides. Deposits of actinides in bone sho uld be minimized because development of osteosarcoma appears to be rel ated to internal exposure. In contrast with other actinides, such as p lutonium or americium where chelating agent treatment is efficient, th e therapeuric approaches used for cases of uranium contamination are w idely ineffective. This is the first report on in vivo efficacy of a c helating 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 ha s been investigated for its ability to remove uranium from rats after intravenous or intramuscular injection as nitrate. Following an immedi ate single intramuscular or intravenous injection of 3,4,3-LIHOPO (30 mu mol . kg(-1)) urinary excretion of uranium was greatly enhanced wit h a corresponding reduction 24 h later in kidney and bone uranium cont ent (to about 20 and 50% of the control rat respectively). Under ident ical experimental conditions, sodium bicarbonate (640 mu mol . kg(-1)) reduced the uranium content in kidney in kidney and bone only to abou t 90 and 70% of controls respectively, and there was less enhancement of uranium excretion. However, when treatment was delayed by 30 min an d administered intraperitoneally, there was no marked difference in re tention and excretion of uranium between the two compounds. As this li gand showed no apparent irreversible toxicity at effective dosages, it is concluded that the administration of the 3,4,3-LIHOPO chelating ag ent represents potentially a most significant advance for prompt treat ment of uranium contamination, while a more detailed investigation