Towards a model of DTPA decorporation therapy

Transcription

1 Towards a model of DTPA decorporation therapy B. Breustedt, KIT, Germany E. Blanchardon, IRSN, France P. Berard, CEA, France P. Fritsch, CEA, France O. Gremy, CEA, France A. Giussani, BfS, Germany M. Kastl, BfS + TUM, Germany D. Nosske, BfS, Germany M.A. Lopez, CIEMAT, Spain KIT University of the State of Baden-Wuerttemberg and National Research Center of the Helmholtz Association

2 Radiopharmaceutical vs. Decorporation Agent Radiopharmaceutical Diagnostic Imaging Injection of RP Metabolism Biokinetics Therapy Pictures taken from: Biersack (ed), Clinical Nuclear Medicine, Springer 2007

3 Radiopharmaceutical vs. Decorporation Agent Decorporation Agent Injection of Decorporation Agent Radiation Dose risk, effect Unintended Intake of Radionuclide Metabolism Biokinetics

4 Radiopharmaceutical vs. Decorporation Agent Decorporation Agent Injection of Decorporation Agent Lower Radiation Dose risk, effect Unintended Intake of Radionuclide Modified Metabolism Biokinetics

5 Radiopharmaceutical vs. Decorporation Agent Dose Assessment Radiopharmaceutical Intake is known Biokinetics is observed (and might be modeled individually) Bq msv Intake Data Biokinetic model Dosimetric model Dose

6 Radiopharmaceutical vs. Decorporation Agent Dose Assessment Radiopharmaceutical Intake is known Biokinetics is observed (and might be modeled individually) Bq msv Intake Data Biokinetic model Dosimetric model Dose Dose Assessment Unintended Intake of Radionuclide Intake is unknown Biokinetics is only modeled (reference model) Bq Bq msv Data Biokinetic model Intake Dosimetric model Dose

7 Radiopharmaceutical vs. Decorporation Agent Dose Assessment Radiopharmaceutical Intake is known Biokinetics is observed (and might be modeled individually) Bq msv Intake Data Biokinetic model Dosimetric model Dose Dose Assessment Unintended Intake of Radionuclide Intake is unknown Biokinetics is only modeled (reference model) Decorporation Agent Modifies Biokinetics Bq??? Bq????? msv Data Biokinetic model Intake Dosimetric model Dose

8 Incorporation of Plutonium and Actinides Plutonium and Actinides mainly encountered in the nuclear fuel cycle Other uses: nuclear batteries (Pu-238), smoke detectors (Am-241), Most Isotopes are long-lived alpha-emitters high equivalent doses after incorporation Incorporation during routine handling procedures (workers) Routine monitoring via radiobioassay (24h urine, 24h feces, lung counting) after releases to environment (population) Emergeny monitoring??? Plutonium and Actinides mainly accumulate in Liver and Skeleton ICRP reference biokinetic models for Respiratory tract and Alimentary tract (generic models) Systemic behaviour Dr. Bastian Breustedt Towards a model of DTPA decorporation therapy

9 Incorporation of Plutonium and Actinides Biokinetic models Example: Inhalation of Plutonium Respiratory Tract (ICRP66) Alimentary Tract (ICRP30) m Systemic Model (ICRP67) Dr. Bastian Breustedt Towards a model of DTPA decorporation therapy Taken from: A.C. James et al., Radiat Prot Dosim, Vol.127, Nos 1-4, p (2007)

10 Incorporation of Plutonium and Actinides Biokinetic models Example: Inhalation of Plutonium Respiratory Tract (ICRP66) Alimentary Tract (ICRP30) m Systemic Model (ICRP67) Dr. Bastian Breustedt Towards a model of DTPA decorporation therapy Taken from: A.C. James et al., Radiat Prot Dosim, Vol.127, Nos 1-4, p (2007)

11 Decorporation Therapy with DTPA DTPA (Diethylene Triamine Pentaacetic Acid) Principle: masking of metal ions In-vivo formation of stable complexes (chelates) Chelates are rapidly eliminated via urine Application: Intakes of Plutonium and Transuranium Elements i.v. infusion of salts of Ca-DTPA or Zn-DTPA Enhancement of urinary excretion for several days reduction of body burden

12 Decorporation Therapy with DTPA DTPA (Diethylene Triamine Pentaacetic Acid) Principle: masking of metal ions In-vivo formation of stable complexes (chelates) Chelates are rapidly eliminated via urine Application: Intakes of Plutonium and Transuranium Elements i.v. infusion of salts of Ca-DTPA or Zn-DTPA Enhancement of urinary excretion for several days reduction of body burden Assessment of disturbed data and evaluation/optimization of therapy requires models that can describe the effect of the DTPA

13 Biokinetic modeling of DTPA therapy Example: The CONRAD/EURADOS Approach Coupling of compartmental models for Undisturbed biokinetics of Actinide ICRP reference model Injected forms of DTPA Reinterpretation of Stather et al Complexes of DTPA with actinide (formed in-vivo) Model Description: Breustedt B et al, Radiation Protection Dosimetry, 134, (2009).

14 Biokinetic modeling of DTPA therapy Example: The CONRAD/EURADOS Approach Coupling of compartmental models for Undisturbed biokinetics of Actinide ICRP reference model Injected forms of DTPA Reinterpretation of Stather et al Complexes of DTPA with actinide (formed in-vivo) Urinary Excretion of USTUR Case 0269 Fit of original CONRAD/EURADOS model Case Description: James AC et al, Radiation Protection Dosimetry, 127, (2007).

15 Biokinetic modeling of DTPA therapy Example: The CONRAD/EURADOS Approach Coupling of compartmental models for Undisturbed biokinetics of Actinide ICRP reference model Injected forms of DTPA Reinterpretation of Stather et al Complexes of DTPA with actinide (formed in-vivo) Urinary Excretion of USTUR Case 0269 Fit of modified CONRAD/EURADOS models Case Description: James AC et al, Radiation Protection Dosimetry, 127, (2007).

16 Biokinetic modeling of DTPA therapy Example: The CONRAD/EURADOS Approach Coupling of compartmental models for Undisturbed biokinetics of Actinide ICRP reference model Injected forms of DTPA Reinterpretation of Stather et al Complexes of DTPA with actinide (formed in-vivo) Urinary Excretion of USTUR Case 0269 Fit of modified CONRAD/EURADOS models Case Description: James AC et al, Radiation Protection Dosimetry, 127, (2007).

17 Biokinetic modeling of DTPA therapy Requirements: Understanding of Undisturbed Radionuclide biokinetics Physiological (interpretation of biokinetic) models Biokinetics of injected forms of DTPA and chelates In-vivo chelation process Location (Intracellular Decorporation?) Competitors (bioligands and metals) and their influence Future Research Needs Studies of (undisturbed) biokinetics of radionuclides Understanding and modeling of physiological processes behind biokinetics Dedicated in-vitro and animal studies (e.g. CEA studies with rats) Studies of in-vivo chelation process Data from inside the system autopsy data (e.g. USTUR) Future option: Optimization of ligands for chelation therapy

18 Karlsruhe Institute of Technology European Radiation Dosimetry Group Thank you for your Attention