Characterization of radiation quality based on nanodosimetry. Hans Rabus

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1 Characterization of radiation quality based on nanodosimetry Hans Rabus Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Germany

2 Motivation Biological effectiveness of ionizing radiation depends on radiation quality Radiation quality is defined as the spectrum of particles and their energies... related to the microscopic particle track structure (and DNA is believed to be the critical target) Defining radiation quality in terms of measurable physical quantities related to particle track structure would enable a unified approach for risk assessment and radiotherapy and the realisation of a measurand Seite 2 von 19

3 Nanodosimetry versus Microdosimetry Cell Nucleus d Measurement quantity: Ionization cluster size ν (number of ionizations) Frequency distribution P (ν d ; Q) Seite 3 von 19

4 Scaling relation for ionization cluster size distributions ionization cross section 1 ρ/ (g cm - ³) mass density σ ρ ion D M = m 1 mol ν = 0 ν P( ν ) mass of molecule nm 1 mm diameter of sensitive volume D Seite 4 von 19

5 Ion-counting nanodosimeter for measuring ionisation cluster size distributions Developed in collaboration with Loma Linda University & Weizmann Institute Source: B. Grosswendt Drift time / µs Source: G. Hilgers Seite 5 von 19

6 Ionization cluster-size distributions Measurement in a gas target equivalent to a DNA segment Probability P (ν Q) α-particles in propane 90 kev 750 kev 20 MeV Cluster size ν Seite 6 von 19

7 Ionisation cluster-size distributions (Monte-Carlo simulations for 4.6 MeV α-particles) Probabilit typ (ν Q) Liquid Water, (Dρ) = 0.4 µg/cm² Nitrogen, (Dρ) = µg/cm² Propane, (Dρ) = µg/cm² σ ρ m ion D = 0.05 mol Const ionisation cluster size ν Adapted from Grosswendt, RPD 110, 789 (2004) Seite 7 von 19

8 Track structure parameters and biological effectiveness 10 0 Pro obability P (ν Q) Charged particle F = 2 ( Q) P( ν Q) ν =2 Cluster size ν δelectron ~ 2 nm Single damage (repairable) base pair DNA segment Clustered damage (irrepairable) Seite 8 von 19

9 F 2 vs. double strand breaks (DSB) in plasmid DNA σ DSB / µm² σ DSB F 2 Helium Lithium Carbon Oxygen Neon Linear energy transfer L in kev/µm Exp. data from Taucher-Scholz and Kraft, Radiat. Res. 151 (1999), simulations by Bernd Grosswendt F Seite 9 von 19

10 Linking nanodosimetry and radiobiology The approach of Gartyet al., PMB 55, 761 (2010) ion ion p SB p SB recombination recombination strand break strand break DSB if on opposite strands Seite 10 von 19

11 Linking nanodosimetry and radiobiology The approach of Gartyet al., PMB 55, 761 (2010) P [ ] ν P( Q) ν ( DSB Q) 1+ ( 1 p ) 2( 1 p 2) = ν ν =2 SB SB Probability for double strand break From data fitting to radiobiological assay ionisation cluster size distribution Nanodosimetric rad. quality factor Q ndos = P P ( DSB Q) ( DSB Q ) ref Seite 11 von 19

12 Radiation quality factors derived from nanodosimetric track structure characteristics 100 Q_ND-p Q_ND-He Q_ND-C Q_ICRP 60 Q( (L) Linear energy transfer L in kev/µm R. Schulte et al. Z. Med. Phys. 18, , 2008 Seite 12 von 19

13 Summary: R&D strategy for nanodosimetry Concerted development of techniques to measure ionisation cluster sizes in macroscopic(mm) gas targets simulate ionisation cluster sizes in nano-volumes(nm) Biophysical models for linking ionisation cluster size distribution and DNA damage probability Seite 13 von 19

14 Challenges and open issues Relevant target size? (DNA segment, histone, cell nucleus) Multi-scale characterisation of track structure? Relevance of DNA cross sections? Relevance of condensed-phase effects? Joint Research Project within the European Metrology Programme Seite 14 von 19

15 EMRP Project "Biologically Weighted Quantities in Radiotherapy" ( ) 6.6, Hans Rabus STAR Wildlife dosimetry workshop, June CIEMAT (Madrid, Spain) Seite 15 von 19

16 Mean ionisation cluster size for DNA-segment target H 2 O DNA Number of ionisations is underestimated when target volume is filled with water! Source: Marion Bug Seite 16 von 19

17 Nanodosimetry - take home messages Different radiation qualities are distinct by the microscopic interaction pattern of the particle track structure. Nanodosimetry characterises radiation quality by measurable physical properties of track structure. Nanodosimetry is based on a density scaling principle that has been verified by simulations and experimentally. Nanodosimetric track structure parameters correlate with yield of early biological endpoints. The EMRP joint research project BioQuaRT studies the relation of nanodosimetry and track structure in a multi-scale approach. Seite 17 von 19

18 Acknowledgements The experimental nanodosimetry team at PTB: Gerhard Hilgers, Wolfgang Helms, Andreas Pausewang, Beate Lambertsen The track structure simulation team at PTB: Heidi Nettelbeck, Marion Bug, Peter Lazarakis(now U Sydney) Our collaborators: Stanislaw Pszona and Aliaksandr Bantsar(NCBJ, Poland) Davide Moro, Paolo Colautti and Valeria Conte (INFN-LNL, Italy) ReinhardSchulte (LLU, USA) Carmen Villagrasa, Sylvain Meylan, Marta Bueno, Davide Bianco(IRSN, France) Anatoly Rosenfeld, Susanna Guatelli(Uni Wollongong, Australia) Andrey Solov yov(uni Frankfurt, Germany) Eugene Surdutovich(Oakland University, USA) The EMRP is jointly funded by the EMRP participating countries within EURAMET and the European Union. Seite 18 von 19

19 Physikalisch-Technische Bundesanstalt Braunschweig und Berlin Bundesallee Braunschweig, Germany Hans Rabus Head, Department 6.6 "Fundamentals of Dosimetry" Phone: Status: Jun 2014