Characterization of radiation quality based on nanodosimetry Hans Rabus Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Germany
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
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
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 10-6 1 nm 1 mm diameter of sensitive volume D Seite 4 von 19
Ion-counting nanodosimeter for measuring ionisation cluster size distributions Developed in collaboration with Loma Linda University & Weizmann Institute Source: B. Grosswendt 0 10 20 30 40 50 60 70 Drift time / µs Source: G. Hilgers Seite 5 von 19
Ionization cluster-size distributions Measurement in a gas target equivalent to a DNA segment Probability P (ν Q) 10 0 10-1 10-2 10-3 α-particles in propane 90 kev 750 kev 20 MeV 10-4 0 20 40 60 80 Cluster size ν Seite 6 von 19
Ionisation cluster-size distributions (Monte-Carlo simulations for 4.6 MeV α-particles) Probabilit typ (ν Q) 0.15 0.10 Liquid Water, (Dρ) = 0.4 µg/cm² Nitrogen, (Dρ) = 0.578 µg/cm² Propane, (Dρ) = 0.321 µg/cm² σ ρ m ion D = 0.05 mol Const. 0.00 0 5 10 15 20 25 30 ionisation cluster size ν Adapted from Grosswendt, RPD 110, 789 (2004) Seite 7 von 19
Track structure parameters and biological effectiveness 10 0 Pro obability P (ν Q) 10-1 10-2 10-3 10-4 2 Charged particle 0 20 40 60 80 F = 2 ( Q) P( ν Q) ν =2 Cluster size ν δelectron ~ 2 nm Single damage (repairable) 10-20 base pair DNA segment Clustered damage (irrepairable) Seite 8 von 19
F 2 vs. double strand breaks (DSB) in plasmid DNA 3 10-2 10 0 σ DSB / µm² 10-2 10-3 10-4 σ DSB F 2 Helium Lithium Carbon Oxygen Neon 10-1 3 10-3 3 10 0 10 1 10 2 10 3 3 10 3 Linear energy transfer L in kev/µm Exp. data from Taucher-Scholz and Kraft, Radiat. Res. 151 (1999), simulations by Bernd Grosswendt F 2 10-2 Seite 9 von 19
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
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
Radiation quality factors derived from nanodosimetric track structure characteristics 100 Q_ND-p Q_ND-He Q_ND-C Q_ICRP 60 Q( (L) 10 1 0.1 1 10 100 1000 Linear energy transfer L in kev/µm R. Schulte et al. Z. Med. Phys. 18, 286-296, 2008 Seite 12 von 19
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
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 http://www.ptb.de/emrp/bioquart.html Seite 14 von 19
EMRP Project "Biologically Weighted Quantities in Radiotherapy" (2012-2015) 6.6, Hans Rabus STAR Wildlife dosimetry workshop, 10-12 June 2014. CIEMAT (Madrid, Spain) Seite 15 von 19
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
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. http://www.ptb.de/emrp/bioquart.html Seite 17 von 19
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
Physikalisch-Technische Bundesanstalt Braunschweig und Berlin Bundesallee 100 38116 Braunschweig, Germany Hans Rabus Head, Department 6.6 "Fundamentals of Dosimetry" Phone: 0531 592-6600 E-Mail: Hans.Rabus@ptb.de www.ptb.de Status: Jun 2014