Dissertation
Development of a new compartmental model for plutonium decorporation therapy
Doctor of Philosophy (PhD), Washington State University
01/2018
Handle:
https://hdl.handle.net/2376/111943
Abstract
Individuals with significant intakes of plutonium (Pu) are typically treated with chelating agents. The trisodium salt form of calcium diethylenetriaminepentaacetate (Ca-DTPA) is a decorporation drug that forms stable complexes with plutonium in-vivo, enhancing its excretion. Since plutonium biokinetics is affected by its complexation with this drug, standard biokinetic models cannot be used to estimate plutonium intake. Prior to this work, only ad hoc solutions were available for modeling plutonium biokinetics during and after chelation therapy. In this study, a new model composed of two linked structures describing the distinct kinetics of the intravenously injected Ca-DTPA and the in-vivo formed Pu-DTPA chelate, was developed, parameterized, and validated. Chelation is assumed to take place in the blood and the extracellular fluids (ECF), including the ECF surrounding the liver, skeleton and soft tissues, portraying a fast and slow kinetics. United States Transuranium and Uranium Registries (USTUR) whole-body donor (Case 0212) was exposed to plutonium via wound and treated extensively with Ca-DTPA. Urine measurements and post-mortem plutonium activities in the liver and the skeleton from Case 0212 were used for model development and initial validation, respectively. The model was implemented in SAAM II® software with the Leggett et al. (2005) plutonium systemic model, the International Commission on Radiological Protection (ICRP) Publication 100 human alimentary tract model, and the National Council on Radiation Protection and Measurements’ Report 156 wound model. The Coordinated Network for Radiation Dosimetry (CONRAD) approach to decorporation modeling was applied by using a chelation constant describing the kinetics of the in-vivo chelation reaction. The model structure was tested with the ICRP Publication 67 and the Luciani and Polig plutonium systemic models. The model’s fitting of urine and autopsy data was compared to the CONRAD model and its optimized version, resulting in both improved goodness-of-fit to the bioassay data, and more accurate predictions of post-mortem plutonium retention. The model was further validated using USTUR Case 0269, who inhaled soluble plutonium and was treated with different chelating agents. The model developed in this work simultaneously fits the chelation affected and non-affected urinary excretion data and predicts autopsy data in major deposition sites.
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Details
- Title
- Development of a new compartmental model for plutonium decorporation therapy
- Creators
- Sara de Souza Zanotta Dumit
- Contributors
- Sergei Y Tolmachev (Advisor)Kathryn E Meier (Committee Member)Jeannie Padowski (Committee Member)Sayed S Daoud (Committee Member)Daniel J Strom (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Pharmacy and Pharmaceutical Sciences, College of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 205
- Identifiers
- 99900581711901842
- Language
- English
- Resource Type
- Dissertation