Biokinetic modelling of DTPA decorporation therapy: the CONRAD approach.
Administration of diethylene triamine pentaacetic acid (DTPA) can enhance the urinary excretion rate of plutonium (Pu) for several days, but most of this Pu decorporation occurs on the first day after treatment. The development of a biokinetic model describing the mechanisms of decorporation of actinides by administration of DTPA was initiated as a task of the coordinated network for radiation dosimetry project. The modelling process was started by using the systemic biokinetic model for Pu from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiation Protection Publication 53. The chelation of Pu and DTPA to Pu-DTPA was treated explicitly and is assumed to follow a second-order process. It was assumed that the chelation takes place in the blood and in the rapid turnover soft tissues compartments of the Pu model, and that Pu-DTPA behaves in the same way as administered DTPA. First applications of this draft model showed that the height of the peak of urinary excretion after administration of DTPA was determined by the chelation rate. However, repetitions of DTPA administration shortly after the first one showed no effect in the application of the draft model in contrast to data from real cases. The present draft model is thus not yet realistic. Therefore several questions still have to be answered, notably about where the Pu-DTPA complexes are formed, which biological ligands of Pu are dissociated, if Pu-DTPA is stable and if the biokinetics of Pu-DTPA excretion is similar to that of DTPA. Further detailed studies of human contamination cases and experimental data about Pu-DTPA kinetics will be needed in order to address these issues. The work will now be continued within a working group of EURADOS.
Forschungszentrum Karlsruhe GmbH, PO Box 3640, D-76021 Karlsruhe, Germany. bastian.breustedt@kit.edu
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Breustedt
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Blanchardon
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Berard
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Fritsch
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Giussani
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Lopez
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Luciani
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Nosske
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Piechowski
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Schimmelpfeng
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D002614:Chelating Agents / Q000627:therapeutic use*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D004369:Pentetic Acid / Q000627:therapeutic use*; D011005:Plutonium / Q000493:pharmacokinetics*; D011832:Radiation Injuries / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*
D002614:Chelating Agents; D011005:Plutonium; D004369:Pentetic Acid