THE USE OF CHELATING AGENTS FOR ACCELERATING EXCRETION OF RADIOELEMENTS
Although the deleterious effects of exposure to ionizing radiation were first recognized and described over fifty years ago, the adequate treatment of these effects still remains a therapeutic challenge. At the present time, when increasing numbers of our population are being exposed to radiation because of the great increase in availability and use of radioactive isotopes and because of the potential exposure of much greater numbers of people to radiation following a possible atomic bomb burst or from disseminated radioactivity, the need for development of adequate therapy is becoming an increasingly pressing medical problem. In a consideration of possible approaches to therapy, one must distinguish between radiation front sources external to the body and radiation which results from radioactive materials which by some means or other have gained access into the body. Internally deposited radiation emitters can be particularly insidious since so many of them become fixed in the skeleton and are eliminated at very slow rates. While it is possible to remove external sources of damaging radiation once the hazard is recognized, the internal radiation emitters often are not readily displaced and the body remains exposed to prolonged continued radiation. Where long-lived elements, such as plutonium with a biological half-life of the order of 100 years or radium with one of 45 years, are involved, the body can be subject to continuous radiation for the remainder of its lifetime. Moreover, because the radiation persists for such long periods of time, only minute amounts of certain radioelements, i.e., plutonium and radium, need have entered initially to produce considerable injury. The effects of this type of chronic exposure to radiation are well documented in the case reports on radium poisoning in workers in the luminous dial industry. The damage is manifest in various forms, i.e., severe anemia, osteitis, and osteogenic sarcoma. In the past, therapy to check injury from internal radiation emitters had been directed to attempts to hasten the elimination of the noxious agent. These have included such methods as low calcium diets, parathormone, viosterol, ammonium chloride, calcium gluconate, and low phosphorus diets. Of these the decalcifying type of treatment was reported to have some measure of effectiveness. The results of the other types of therapy were equivocal. The most successful approach was reported in the work of Schubert. Using zirconium citrate complex, administered 3 hours after the injection of radioyttrium and plutonium into rats, he was able to increase the urinary excretion of the injected radio elements many times over that of the excretion in the untreated rats, in some instance up by a factor of 50 for the first day of excretion. However, when used at later time periods, i.e., in a dog at 150 days, the increase in urinary excretion was only a factor of 2 to 3 over the control period. The fecal excretion of the radio elements was not influenced by the treatment. The present study reports a different approach for accelerating the excretion of radioelements, namely the use of chelating agents. Many of the rare earth and actinide series of elements form water-soluble chelates with various organic compounds. This consideration suggested the possibility that this property of chelating agents might be used 'in vivo' to mobilize radio elements fixed within the body. Of the many compounds considered, ethylenediamine tetracetic acid (EDTA) was chosen for this study. The EDTA was selected because it forms a very stable chelate with many metal ions and hence has a strong tendency to remove such ions from insoluble combinations, i.e., it will dissolve such salts as calcium oxalate, barium sulfate, and lead phosphate in neutral and alkaline solutions. Moreover, it has suitable characteristics for 'in vivo' application. It forms serum soluble chelates which are not readily broken down in the body but are rapidly excreted intact via the kidney. It is readily absorbed through the digestive tract. It has a very low level of toxicity when used as described in this study, namely as the calcium complex. A dose equivalent to 3 grams per kilo of body weight, injected intraperitoneally into rats, will result in death in approximately 50% of the injected animals in one day. When administered as a neutral salt, the EDTA combines avidly with serum calcium and produces death in hypocalcemia with relatively small doses, i.e., approximately 200 milligrams per kilo of body weight in rats. However, when administered combined with an equivalent weight of calcium ion, this negative calcium balance is prevented and the compound is rendered relatively non-toxic. Under these conditions the EDTA will still chelate a large number of metals, namely the metals which displace the calcium from combination with the EDTA because they form more stable chelates.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- Physics Division
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 1001062
- Report Number(s):
- UCRL-1351; TRN: US201102%%398
- Country of Publication:
- United States
- Language:
- English
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