Learning Objectives Review of the Radiobiological Principles of 1. To understand the radiobiological basis Radiation Protection of radiation protection standards. 2. To define the radiation protection magnitudes and units, their values and their practical measurement. Cari Borrás, D.Sc., FAAPM, FACR Radiological Physics and Health Services Consultant 3. To distinguish between stochastic and Washington DC, USA deterministic effects. 1 2 Interaction of ionizing radiation with Radiation Effects DNA, the critical target Ionizing radiation cell nucleus interacts at the cellular level: • ionization • chemical changes incident • biological effect radiation chromosomes DIRECT ACTION INDIRECT ACTION http://rpop.iaea.org/ 3 http://rpop.iaea.org/ 4 Indirect action of radiation Direct action of radiation Consider water + H2O H2O + e • Predominant for high LET radiation, particulates Water molecule becomes ionized to a free radical (unpaired electron) and an ion (loss of an electron). These are highly reactive, short lifetime • High LET radiations interact predominately with nuclei H O+ + H O H O+ + OH 2 2 3 • setting in motion more protons and other heavier nuclear particles • diffusion distance twice diameter of DNA helix • estimated 2/3 of x-ray damage in mammalian cells from • smaller particles (electrons) are produced which cause indirect damage but this is less significant c.f. direct action hydroxyl radicals • less indirect action for high LET radiation • chemical sensitizers exploit indirect damage • Not modified by sensitizers or protectors • protectors act against radicals http://rpop.iaea.org/ 5 http://rpop.iaea.org/ 6 Outcomes after Cell Exposure DNA Damage Radiation hits cell Unviable Cell There are qualitative and quantitative nucleus! Cell dies differences in initial DNA damage caused by radiation Cell mutates DNA damage caused by radiation exhibits multiply damaged but mutation Viable Cell sites and clustered legions is repaired Double strand breaks are more common in radiation-induced damage than single strand breaks, which are more common Cancer? in normal endogenous DNA damage. Cell survives but mutated http://rpop.iaea.org/ 7 http://lowdose.energy.gov/pdf/Powerpoint_WEBBystander.pdf 8 10-15 Energy deposition How does radiation interact Excitation/ionization PHYSICAL INTERACTIONS -12 with cells? 10 Initial particle tracks Radical formation 10-9 Diffusion, chemical reactions PHYSICO-CHEMICAL INTERACTIONS 10-6 Initial DNA damage ) Past Theory Present Theories c e s ( -3 DNA breaks / base damage Hit theory Bystander effects E 10 1 ms M I T 100 1 second Radiation causes free Radiation causes free Repair processes radicals to damage only radicals to trigger cell-cell Damage fixation Timing of communication and cell- 103 BIOLOGICAL RESPONSE the cell that is “hit” by 1 hour Cell killing matrix communication to events direct ionization 1 day Mutations/transformations/aberrations cells other than those 6 10 Proliferation of "damaged" cells which are “hit” by the 1 year Promotion/completion leading to direct ionization. 109 Teratogenesis MEDICAL EFFECTS radiation Cancer effects. 100 years Hereditary defects http://lowdose.energy.gov/pdf/Powerpoint_WEBBystander.pdf 9 10 The 2007 (ICRP 103) Recommendations RP Dosimetric Quantities and Units ▲ ICRP reviewed new radiobiology data since 1991 ▲ Incorporate Exposures ▲ Changed • External • Radiation-weighting factors (w ) R • Internal • Tissue-weighting factors (wT) • Risk of cancer induction rather than mortality ▲ Are Different For: ▲ Did not change • Low doses of (low-LET) radiation < 0.5 Gy • Radiation protection principles, (i.e. LNT) o Stochastic (probabilistic) effects, LNT is applicable • Dose limits • Cancer induction • Radiation quantities and units, accepting ICRU • Hereditary diseases operational quantities for compliance with dose limits High doses of radiation ▲ Emphasized dose constraints • o Tissue reactions (deterministic effects), threshold exists 11 12 RP Dosimetric Quantities and Units RP Dosimetric Quantities and Units Stochastic Effects Tissue Reactions Evolution of Terminology Dose to Tissue = Absorbed Dose * RBE (Gy) ICRP 26 (1977) ICRP 60 (1991) ICRP 103 (2007) # RBE : radiobiological effectiveness * Equivalent Dose Equivalent Dose differs for Effective Dose Effective Dose Effective Dose Equivalent • different biological endpoints and • different tissues or organs * No specific term # Radiation Weighted Dose proposed but not accepted The SI unit is J kg-1 and the special name is sievert (Sv) 13 14 RP Dosimetric Quantities and Units Radiation Weighting Factors (ICRP 103) Stochastic Effects (Sv) Equivalent Dose, H , in a tissue T: Radiation type and energy range wR T Photons 1 Electrons and muons 1 HT = ΣR wR D T,R Protons (1991, 2007), pions (2007) 2 wR is the radiation weighting factor, which accounts for Alpha particles, fission fragments, heavy ions 20 the detriment caused by different types of radiation Neutrons, energy < 10 keV Continuous Function relative to photon irradiation 10 keV to 100 keV D T,R is the absorbed dose averaged over the tissue > 100 keV to 2 MeV T due to radiation R > 2 MeV to 20 MeV wR values are derived from in vivo and in vitro RBE studies > 20 MeV They are independent of dose and dose rate in the low dose region 15 16 RP Dosimetric Quantities and Units Stochastic Effects (Sv) Effective Dose, E E = ΣT wT H T = ΣT ΣR wT wR D R,T wT represents the relative contribution of that tissue or organ to the total detriment resulting from uniform irradiation of the body ΣT wT = 1 A uniform dose distribution in the whole body gives an effective dose numerically equal to the radiation- weighted dose in each organ and tissue of the body 17 18 Tissue Weighting Factors RP Dosimetric Quantities and Units (ICRP 103) Tissue w ∑ w T T ▲ Incorporate Exposures Bone-marrow (red), Colon, Lung, Stomach, Breast, 0.12 0.72 • External Remainder Tissues* • Internal Gonads 0.08 0.08 Bladder, Oesophagus, Liver, Thyroid 0.04 0.16 Bone surface, Brain, Salivary glands, Skin 0.01 0.04 So far we have discussed external exposures Total 1.00 Let´s see about exposures from radionuclides * Remainder Tissues: Adrenals, Extrathoracic region, Gall bladder, Heart, Kidneys, Lymphatic nodes, Muscle, Oral mucosa, Pancreas, Prostate, Small intestine, Spleen, Thymus and Uterus/cervix 19 20 RP Dosimetric Quantities and Units RP Dosimetric Quantities and Units Activity, A Stochastic Effects (Sv) The activity A of an amount of a radionuclide Committed Equivalent Dose in particular energy state at a given time t is For radionuclides A = d N / d t incorporated in the body where d N is the expectation value of the where τ is the integration time following the intake at time t0 number of spontaneous nuclear transitions from that energy state in the time interval d t Committed Effective Dose τ The SI unit of activity is the Becquerel (Bq) Adults: 50 y Children: 70 y 1 Bq = 1 s-1 21 22 Limitations of RP Operational Quantities - ICRU Equivalent and Effective Doses Dose Equivalent, H ▲ Are not directly measurable H = Q * D (Sv) ▲ Point quantities needed for area monitoring (in Where: D = Absorbed Dose a non-isotropic radiation field, effective dose Q = Quality Factor, function of L (LET) depends on the body’s orientation in that field) ∞ ▲ Instruments for radiation monitoring need to be calibrated in terms of a measurable quantity for which calibration standards exist At a point in tissue: Where: DL is the distribution of D in L for the charged Operational protection quantities are needed! particles contributing to D 23 24 Assessment of Effective Dose from Individual Monitoring Data • Hp (10) personal dose equivalent from external exposure H*(10) and H (10) – photons > 12 keV and neutrons P • ej,inh(τ) is the committed effective dose coefficient for activity intakes by inhalation of radionuclide j HP (0.07) – α and β particles and doses to extremities • Ij,inh is the activity intake of radionuclide j by inhalation • ej,ing(τ) is the committed effective dose coefficient for Ω in RP usually not specified. Instead, activity intakes of radionuclide j by ingestion Maximum H’(0.07, Ω) is obtained • Ij,ing is the activity intake of radionuclide j by ingestion by rotating meter seeking maximum reading 25 26 RP Dosimetric Quantities and Units System of Quantities for Radiological Protection Stochastic Effects Absorbed dose, D Collective Effective Dose, S Dose Quantities Operational (due to Individual Effective Doses E and E ) 1 2 defined in the body Quantities For external exposure Equivalent dose, HT, in an organ or tissue T Dose quantities for area monitoring individual monitoring Effective dose, E • d N / d E : number of individuals who experience For internal exposure an effective dose between E and E + d E Committed doses, Activity quantities in • ΔT specifies the time period within which the HT (τ) and E(τ) combination with effective doses are summed Collective effective dose, S biokinetic models and 27 computations 28 RP Dosimetric Quantities and Units E is calculated averaging gender, age and individual sensitivity Caveats Effective Dose should not be used for ▲ Retrospective dose assessments ▲ Estimation of specific individual human exposures and risks ▲ Epidemiological studies without careful consideration of the uncertainties and limitations of the models and values used ICRP 29 30 RP Dosimetric Quantities and Units Effective Dose vs Organ Doses Caveats in Medical Exposures Dose to Individuals Effective Dose is an adequate parameter Absorbed doses to organs or tissues should be used