MELODI2014 Workshop Barcelona, Spain. October 6-9, 2014 MELODI 2014: Integrating observational and experimental research Parallel Session 3: Dosimetry - Microdosimetry-Nanodosimetry from track structures to early billogical effects on DNA. (Carmen Villagrasa, IRSN, France) - Internal contamination (Augusto Giussani, BfS, Germany) - Biological Dosimetry (JF Barquinero, UAB, Spain) DISCUSSION: - How to contribute / improve MELODI SRA regarding dosimetry?  Synergisms between MELODI and EURADOS SRAs. M.A. Lopez, MELODI2014 Barcelona, October 6-9, 2014 1 MELODI2014 Workshop Barcelona, Spain. October 6-9, 2014 Micro- & Nano-dosimetry: from track structure to early biological effects on DNA (C. Villagrasa, IRSN)  Experimental and simulation techniques are being developed/improved to determine the parameters in the physical and chemical interaction of ionizing radiation on biological matter resulting in undesirable biological effects. effects  Nanodosimetric measurements Which is the target volume relevant for studying the biological response? It depends of the biological end-point Cellular u a sca scale: e micrometer c o ete  Ce  Sub-cellular scale (e.g. DNA): nanometer nm scale εi Track structure investigation - Jet Counter (NCBJ), (NCBJ) StarTrack (INFN) and Ion Counter (PTB) - Measurement of the frequency distributions of ionization cluster size in a gas (equivalence with water is fulfilled) M.A. Lopez, MELODI2014 Barcelona, October 6-9, 2014 2 Nanodosimetry : Track structure simulations using Monte Carlo Physical interaction with target molecules 10-18s Radicals Radicals diffusion creation ti 10-15s 10-12s 10-10 s Physical stage Physicochemical h i l stage Repair Biological effects: processes, DSB aberrations DSB, aberrations, enzymatic 10-6s processes 1s-1h mutations …. ……. Chemical reactions Chemical stage Biochemical stage t g Biological stage Simulation The simulation of the first stages used the Geant4-DNA MC code capabilities improved with new BioQuaRT data and methods. New molecular DNA descriptions are used in the MC simulation Biological g data are measured by BioQuaRT team using microbeam facilities (PTB, Surrey university). Early DNA damages results 3 3 MELODI2014 Workshop Barcelona, Spain. October 6-9, 2014 Assessment of internal dose after intakes of radionuclides (A. Giussani, BfS) Extrinsic removal Inhalation Exhalation  Biokinetic Model: metabolic behaviour of contaminants inside the body Skin Ski after the intake Respiratory t tract t model Lymph nodes Direct absorption Sweat  Evaluation of doses from Intake: Dosimetric Models (ICRP Dose coefficients) Ingestion Subcutaneous S b t tissue Transfer compartment t t Liver Gastrointestinal t tract t model  Wound Assessment of the Committed Effective Dose E(50) : Kid Kidney E(50) mSv = I(Bq) * e(50)(mSv/Bq) Skin Other where I(Bq) isorgans the intake Urinary bladder e(50) (50) mSv/Bq S /B is i the th dose d coefficient ffi i t (ICRP) = committed effective dose when Intake is 1 Bq Urine Faeces4 MELODI2014 Workshop Barcelona, Spain. October 6-9, 2014 Assessment of internal dose after intakes of radionuclides (A Giussani, (A. Giussani BfS) Some issues for discussion: - - Models are very complex and data are difficult or imposible to obtain Different types of applications (dose coefficients, bioassay retention and d excretion ti functions,…) f ti ) have h diff different t requirements i t off accuracy and realism Example: Iodine Model is ok, but embrio/fetus needs a more detailed modeling Importance of UNCERTAINTY and SENSITIVITY ANALYSIS: work under development p on - EURADOS WG7 - CURE Project (multidisplinary action where Epidemiologists, Radiobiologists and Dosimetrists work together) 5 MELODI2014 Workshop Barcelona, Spain. October 6-9, 2014 Usefulness and limits of Biological dosimetry (JF Barquinero, UAB)  To assess dose due to a possible overexposure to ionizing radiation based on a biological endpoint. Different scenarios: Blood sampling Retrospective 500mGy- 5 Gy 100-500 mGy <100 mGy Exposurre Dose > 5 Gy Recent Damage in DNA Whole bod Whole-body Partial-body Highly localized Highly-localized People involved One or few M.A. Lopez, MELODI2014 Barcelona, October 6-9, 2014 Tens Hundreds Thousands Joan-Francesc BARQUINERO 6 Usefulness and limits of Biological dosimetry (JF Barquinero, UAB) <100 mGy 100-500 100 500 mGy 500mGy- 5 GyGy > 5 NO YES YES NO Detection limits - low doses dic/cells 2/500 Confounding factors: 4/1000 Previous exposures to IR not 6/1500 related to the accident, CT scans…. • dose estimation 95% confidence dose limits ((mGy) y) 100 0 300 100 100 0 5 290 270 Dicentric scoring still remains de most sensitive method, most frequently used and the best biological method for dose evaluation  But! It is time consuming.  To respond to a mass casualty event: NETWORKING Harmonization is required: RENEB Project Network of Biodosimetry labs 7 MELODI2014 Workshop Parallel session 3: DOSIMETRY From MELODI PRIORITIES: PRIORITIES  Characterization of spatial and temporal energy deposition events (track structure and dose rate) and their role in in lowdose radiation responses (e.g. examination of radiation damage).  Relationships between radio- and chemical toxicity and their respective influence on radiation-induced effects resulting from incorporation (internal contamination) of radionuclides radionuclides.  Identification, development and validation of biomarkers for radiation induced health (cancer and non-cancer) effects  Consolidation of major cohorts suitable for epidemiological studies From EURADOS SRA: • To improve understanding of spatial correlations of radiation interaction events • To quantify correlations between track structure and radiation damage – • To better understand biokinetics & dosimetry of internal emitters • Radiological emergencies: To identify and characterize new markers of exposure p and suitable biological end-points for internal exposures • Towards Improved p Radiation Risk Estimates deduced from Epidemiological Cohorts. To explore exposure pathways not yet considered or validated (eye lens, brain heart arteries/walls) brain, 8 MELODI2014 Workshop Barcelona, Spain. October 6-9, 2014 - Microdosimetry-Nanodosimetry Internal Dosimetry Biological Dosimetry  Can contribute to answer common questions of MELODI and EURADOS SRAs  Contribution C t ib ti t MELODI SRA - INTERNAL DOSIMETRY: to DOSIMETRY - Improvements needed in current biokinetic models to better understand non-cancer effects of internal emitters: e.g. vascular diseases - To improve fisiological approach, e.g. to introduce heart arteries/walls for the assessment of the dose to blood, that could be compared with dose assessments of biological dosimetry M.A. Lopez, MELODI2014 Barcelona, October 6-9, 2014 9