The CONRAD approach to biokinetic modeling of DTPA decorporation therapy.
Diethylene Triamine Pentaacetic Acid (DTPA) is used for decorporation of plutonium because it is known to be able to enhance its urinary excretion for several days after treatment by forming stable Pu-DTPA complexes. The decorporation prevents accumulation in organs and results in a dosimetric benefit, which is difficult to quantify from bioassay data using existing models. The development of a biokinetic model describing the mechanisms of actinide decorporation by administration of DTPA was initiated as a task in the European COordinated Network on RAdiation Dosimetry (CONRAD). The systemic biokinetic model from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiological Protection Publication 53 were the starting points. A new model for biokinetics of administered DTPA based on physiological interpretation of 14C-labeled DTPA studies from literature was proposed by the group. Plutonium and DTPA biokinetics were modeled separately. The systems were connected by means of a second order kinetics process describing the chelation process of plutonium atoms and DTPA molecules to Pu-DTPA complexes. It was assumed that chelation only occurs in the blood and in systemic compartment ST0 (representing rapid turnover soft tissues), and that Pu-DTPA complexes and administered forms of DTPA share the same biokinetic behavior. First applications of the CONRAD approach showed that the enhancement of plutonium urinary excretion after administration of DTPA was strongly influenced by the chelation rate constant. Setting it to a high value resulted in a good fit to the observed data. However, the model was not yet satisfactory since the effects of repeated DTPA administration in a short time period cannot be predicted in a realistic way. In order to introduce more physiological knowledge into the model several questions still have to be answered. Further detailed studies of human contamination cases and experimental data will be needed in order to address these issues. The work is now continued within the European Radiation Dosimetry Group, EURADOS.
Breustedt
Bastian
B
Institute for Radiation Research, Karlsruhe Institute of Technology, P.O. Box 3640, D-76021 Karlsruhe, Germany. Bastian.Breustedt@kit.edu
Blanchardon
Eric
E
Bérard
Philippe
P
Fritsch
Paul
P
Giussani
Augusto
A
Lopez
Maria Antonia
MA
Luciani
Andrea
A
Nosske
Dietmar
D
Piechowski
Jean
J
Schimmelpfeng
Jutta
J
Sérandour
Anne-Laure
AL
D001822:Body Burden; D002250:Carbon Radioisotopes; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology; D003666:Decontamination; D006801:Humans; D008196:Lymph / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D004369:Pentetic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D011005:Plutonium / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011832:Radiation Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D011874:Radiometry / Q000379:methods*; D012062:Relative Biological Effectiveness; D013194:Staining and Labeling
D002250:Carbon Radioisotopes; D002614:Chelating Agents; D011005:Plutonium; D004369:Pentetic Acid