Effectiveness of DTPA treatments following the injection of particulate plutonium.
A limited long-term experiment has been completed in which the chronic toxicity resulting from a single intravenous injection of 31.4 kBq of a poly-disperse 239Pu colloid sol per kg of body weight was tested in Beagle dogs. The Pu deposited mostly in the phagocytic cells of liver, spleen and to a lesser degree in lung and bone marrow. Slow solubilization of the Pu particles by endogenous ligands caused translocation of the nuclide and redeposition mostly as monomeric Pu in the skeleton and in liver hepatocytes. Thus, the deposit behaved as expected from a pulmonary or wound contamination in humans with a moderately soluble depot of Pu such as Class W hot particles. Therefore, this type of deposit provided the basis for a practical model to study the ensuing radiation effects under various experimental conditions. The dogs were divided into three groups of four animals each, and the following conditions were applied: (a) no further treatment was given, allowing free translocation of the Pu to its secondary deposition sites; (b) interception of the Pu translocation by weekly injections of 30 mumol of Ca-DTPA/kg of body weight (Ca-chelate of diethylene-triaminepentaacetic acid); and (c) interception of translocation by daily injections of 30 mumol/kg body weight of Zn-DTPA. For each of the groups (b) and (c), three dogs were used in a lifetime study, and one was sacrificed for nuclide distribution studies. Free translocation and subsequent deposition in the skeleton resulted in the death of each of the non-chelated dogs from osteosarcoma between 1267 and 1594 days after injection. Weekly treatment with Ca-DTPA reduced the total Pu burden significantly, but these dogs also died with osteosarcoma between 1462 and 1783 days. Daily injections with Zn-DTPA reduced the total Pu burden more efficiently than Ca-DTPA and prevented continuous deposition of solubilized Pu on bone surfaces. The mean post-injection survival of these dogs was 3520 days or about 2.1 times that of the animals receiving Ca-DTPA, while the latent period for bone tumour induction was about 2.6 times longer. This treatment reduced the severity of liver lesions and eliminated the occurrence of persistent leukopenia, but it did not prevent the formation of bone cancer.
Division of Radiobiology, School of Medicine, University of Utah, Salt Lake City 84112.
F W
FW
Bruenger
D M
DM
Taylor
G N
GN
Taylor
R D
RD
Lloyd
D000818:Animals; D001859:Bone Neoplasms / Q000209:etiology* / Q000517:prevention & control; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004285:Dogs; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000517:prevention & control; D004369:Pentetic Acid / Q000627:therapeutic use*; D011005:Plutonium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects
D011005:Plutonium; D004369:Pentetic Acid