Radiobiology

1. Radiobiology

2. Course content • Physical effect of radiation - ionization and excitations - interaction between moving charged particle and stationary electron - stopping power and range of radiation in the medium • Radiation chemistry - physical events - radiolysis of water

3. Effect of radiation on DNA molecules and chromosomes • Cell survival curve - cell death - intrinsic cellular radiosensitivity - cell survival and repair • Radiation effect on normal tissue - from cellular effect to tissue damage - late effect • The effect of radiation on tumors, the biological bases of radiotherapy

4. Hypoxic cells and their importance in radiotherapy - the oxygen effect - the hypoxic cells - methods of selectively attaching hypoxic cells

5. Introduction • Scientists have studied radiation for over 100 years and a great deal of information is known about it. • Radiation is part of nature. All living creatures, from the beginning of time, have been, and are still being, exposed to radiation. We Live (And Have Always Lived) in a “Sea of Radiation”

6. Definition of Radiation • “Radiation is an energy in the form of electro-magnetic waves or particulate matter, traveling in the air.”

7. Ionizing Radiation • Definition: “ It is a type of radiation that is able to disrupt atoms and molecules on which they pass through, giving rise to ions and free radicals”.

8. Basic Model of a Neutral Atom. • Electrons (-) orbiting nucleus of protons (+) and neutrons. Same number of electrons as protons; net charge = 0. • Atomic number (number of protons) determines element.  • Mass number (protons + neutrons)

9. Radioactivity • If a nucleus is unstable for any reason, it will emit and absorb particles. There are many types of radiation and they are all pertinent to everyday life and health as well as nuclear physical applications.

10. Ionization - Ionizing radiation is produced by unstable atoms. Unstable atoms differ from stable atoms because they have an excess of energy or mass or both. - Unstable atoms are said to be radioactive. In order to reach stability, these atoms give off, or emit, the excess energy or mass. These emissions are called radiation.

11. TYPES OF RADIATIONS

13. Types of Radiation

14. Absorbed Dose • Depends on: • Whether material is inside or outside body • How long material remains in the body • How much radioactive material there is • The type of radiation it emits • What its half-life is

15. Natural and Man-Made Radiation Sources

16. Natural Background Radiation • Cosmic Radiation • Terrestrial Radiation • Internal Radiation

17. Cosmic Radiation • The earth, and all living things on it, are constantly being bombarded by radiation from outer space (~ 80% protons and 10% alpha particles). • Charged particles from the sun and stars interact with the earth’s atmosphere and magnetic field to produce a shower of radiation. • The amount of cosmic radiation varies in different parts of the world due to differences in elevation and to the effects of the earth’s magnetic field.

18. Terrestrial Radiation (Uranium, Actinium, Thorium decay series) • Radioactive material is found throughout nature in soil, water, and vegetation. • Important radioactive elements include uranium and thorium and their radioactive decay products which have been present since the earth was formed billions of years ago. • Some radioactive material is ingested with food and water. Radon gas, a radioactive decay product of uranium is inhaled. • The amount of terrestrial radiation varies in different parts of the world due to different concentrations of uranium and thorium in soil.

19. Internal Radiation • People are exposed to radiation from radioactive material inside their bodies. Besides radon, the most important internal radioactive element is naturally occurring K-40, but uranium and thorium are also present as well as H-3 and C-14. • The amount of radiation from potassium-40 does not vary much from one person to another. However, exposure from radon varies significantly from place to place depending on the amount of uranium in the soil. • On average, in the United States radon contributes 55% or all radiation exposure from natural and man-made sources. Another 11% comes from the other radioactive materials inside the body.

20. Man-Made Radiation • Radioactive material is used in: • Medicine - diagnostic (X-ray, CAT) • Medicine - therapeutic (Co-60, Linac) • Medical research (radio-pharmaceuticals, accel.) • Industry - (X-ray density gauges, well logging)

21. Radiation in Medicine • Radiation used in medicine is the largest source of man-made radiation. • Most exposure is from diagnostic x-rays.

22. Man-Made Radiation Sources • Exposure of selected groups of the public: • diagnostic radiology (X-rays) • nuclear medicine (radiopharmaceuticals) • radiotherapy (Co-60)

23. Interaction of radiation with matter

24. Outgoing photon Incoming photon Elastic Scattering No loss of photon energy hnin = hnout

25. e/r  Z2/(hn)2 Elastic Scattering • Elastic scattering is also known as called “Coherent” or “Rayleigh” scattering • Photon scattering angle depends on Z and hn* hn 0.1 MeV 1 MeV 10 MeV Al 15o 2o 0.5o Pb 30o 4o 1.0o • Occurs mainly at low energies • Large Z materials • Contributes nothing to KERMA or dose, no energy transferred, no ionisation, no excitation • No real importance in radiotherapy * F. H. Attix, Introduction to Radiological Physics and Radiation Dosimetry

26. Outgoing electron The Photoelectric Effect Incoming photon Ee = hn - W Ee: maximum kinetic energy of the outgoing electron W: energy needed to remove electron

27. Characteristic X-ray Auger electron The Photoelectric Effect • Photoelectron emitted leaving atom in unstable, excited state • Atom relaxes by • X-ray emission • Auger electron emission (The Auger Effect)

28. t/r Z3/(hn)3 The Photoelectric Effect • Process = attenuation and absorption • Interaction of a photon with bound atomic electrons • Total absorption of photon energy • Photoelectron emitted , max. kinetic energy: Ee = hn - W • Produces characteristic X-rays and/or Auger electrons • Predominates at low energies • Is highly Z dependent • Example: tPb/rPb is 300 times greater than tbone/rbone

29. The Photoelectric Effect • If the photon energy is • slightly higher than the • energy required to remove an • electron form a particular shell • (e.g. K, L, M) around the • nucleus, there is a sharp • increase in t/r. • This increase is called an • absorption edge.

30. K K - - edge for W edge for W K K - - edge for La edge for La Z=74 Z=74 Z=57 Z=57 absortpion absortpion coefficient coefficient CaWO4 Intensifying Screen Mass Mass LaOBr Intensifying Screen 20 20 40 60 80 40 60 80 Photon energy Photon energy keV keV The Photoelectric effect Absorption edges important: 1. In radiology because it influences the choice of material used in intensifying screens, photographic film, contrast agents Example • 2. In radiation protection because it influences the choice of • shielding materials • In radiotherapy because it influences the choice of filtering • material

31. The Photoelectric Effect • Number of X-rays produced/no. of vacancies = Fluorescent Yield (w) • Fluorescent Yield is high for high Z, low for low Z • Low Z materials give low energy X-rays => X-rays absorbed locally • For low Z materials, Auger electrons more probable Fluorescent yield (K-shell vacancy)* * H. Johns & J. Cunningham, The Physics of Radiology, 4th Edition

32. The Compton Effect Outgoing electron Incoming photon f q Outgoing photon

33. The Compton Effect • Interaction of photon with unbound atomic electrons • Scatter + partial absorption of photon energy • Scattered electron + scattered photon • Change in photon wavelength depends on angle of scattered photon lout- lin = constant x (1- Cos q) • lin: wavelength of the outgoing electron, lout: energy of incoming photon • If photon makes a direct hit: • Electron will be scattered straight on with maximum energy • Photon will be scattered backwards i.e. q = 180o with minimum energy • Scattered photon energy

34. The Compton Effect

35. The Compton Effect

36. The Compton Effect • Dominates over a wide range of X-ray energies • Depends on electron density (re) • Independent of Z /r  e / hn

37. Outgoing Electron, E- Incoming Photon, hn Outgoing Positron, E+ Pair Production – Type 1 • hn³ 1.022 MeV • hn – 1.022 = E- + E+ • E-, E+ are the kinetic energies of the electron and positron resp.

38. k/r  Z2 / ln(hn) Pair Production – Type 1 • Photon interacts with Coulomb field of atomic nucleus and is absorbed • Electron/Positron pair produced if hn³ 1.022 MeV • Example of conversion of energy into mass: E = mc2 • Energy equivalent of one electronic mass is 0.511 MeV • As e+ & e- produced, incoming photon must have energy: 2 x 0.511 MeV • e+ and e- can receive any fraction of photon energy • Dominates at high photon energies • Dependent on Z

39. 0.511 MeV photon slow e+ free electron 0.511 MeV photon Pair Production – Type 1 • e+ produced in Pair Production dissipates energy locally • Energy lost through excitation and ionisation of atoms along its track until it comes to rest • It is annihilated by combining with a free electron producing two photons of energy 0.511 MeV

40. Outgoing Electron, E2- Original Electron, E1- Incoming Photon hn > 2.04 MeV Outgoing Positron, E+ Pair production –Type 2 • Otherwise called Triplet Production • Incident photon interacts with Coulomb field of atomic electrons & is absorbed • Incident photon transfers energy to Host e- and e-/e+ pair produced • Conservation of momentum => threshold energy for this process is 4mc2 hn=1.022 MeV+E1-+E2-+E+

41. Summary Pb, W Sn Zr Ca Al H

42. Photonuclear Interactions • High energy photon interacts with atomic nucleus resulting in emission of a proton (p) or a neutron (n) • Occurs for incident photons with energy > few MeV • If p emitted, effect can contribute to dose. But relative importance is low • If n emitted, there can be consequences for radiation protection • must take account in shielding designs • n can escape shielding more readily than photons • n may activate accelerator hardware e.g. in target • Biological effect in radiotherapy patient negligible compared with effects of photons

43. hole hole hole K K K L L L M M M The Auger Effect (Revisited) Auger e- X-ray • Mono-energetic Auger electrons will carry away any surplus energy of excited atom • Multiple Auger electrons can be emitted resulting in an Auger shower. • Vacancies continue to move to less tightly bound shells until they are eventually filled by conduction band (free) electrons K L M E = hn - EM E = EK – EL - EM hn = EK-EL holes in L- and M-shell Initial state: hole in K-shell

44. V Scattered Radiation • = By-product of the interaction of radiation with matter • Scattered radiation = radiation (particulate or EM radiation) that has changed direction with or without a change in energy during its passage through intervening matter. • EXAMPLE: In radiotherapy, scattered radiation comes from the interaction of the primary beam with the flattening filters, primary and secondary collimators, monitor chamber, the patient.

45. 10 keV 100 keV Scattering point Not to scale Scattered Radiation • If energy of incoming radiation high  scatter mostly in forward direction. Example: Therapy range (MV) • If energy of incoming radiation low  scatter in backwards direction (= backscatter) increases. Example: Therapy range (50 – 160 kV) or Diagnostic Imaging (typically 40 – 80 kVp) Spatial distribution of scattered x-rays

46. Scattered Radiation Effects of Scattered Radiation: • In imaging it acts as a mask over the image. • In radiotherapy, adds to patient dose and has radiation protection • issues for staff

47. Secondary Electrons • When primary radiation interacts with matter, electrons may be produced – these electrons are called “secondary electrons” • Secondary electrons are emitted close to the original point of interaction. • If the secondary electron is given enough energy, it can create its own separate track depositing energy along the way – d-ray • d-rays do not deposit energy in the immediate vicinity  consequences for determining Absorbed Dose • NOTE: Electrons follow tortuous paths undergoing many interactions before coming to a stop. Photons travel in straight lines.

48. Medium A: starting point for secondary e- B: stopping point for secondary e- A Incoming Radiation B Range Range versus Energy • The furthest distance radiation travels in a medium is called “the range”. An electron follows a tortuous path undergoing many interactions before coming to a stop

49. Range versus Energy • The range depends on: • the type and energy of the radiation • the density of the traversing medium EXAMPLE: Electron range in tissues Data from: F. Attix, Introduction to Radiological Physics and Radiation Dosimetry

50. Linear Energy Transfer • The LET is the rate at which energy is transferred to the medium and therefore the density of ionisation along the track of the radiation. • LET also referred to as “restricted stopping power” (LD) • LET is expressed in terms of keV per micron dE = energy lost by radiation dX = length of track • Radiation that is easily • stopped has a high LET and • vice versa