01. Biological effects (7,287 KB)

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  • The figure is a theoretical calculation showing the efficiency of the repair capability. Certain enzymes are checking the DNA strings and initiate a repair process.
  • Another example. These are obviously only rough estimates - however they may illustrate the magnitude of the problem. It could be pointed out that 1mGy is of the order of magnitude of the annual exposure of humans. Therefore the whole discussion above could be made for 1 year of life.
  • The image illustrates the differences in ionization densities and distribution between low LET radiation (photons) and high LET radiation (neutrons). Electrons or beta-particles will be somewhere in between
  • The figure illustrates the connection between the primary effects of ionizing radiation and the clinical observable deterministic and stochastic effects. The time between the physical interaction and the detection of e.g. a cancer may be discussed.
  • The fisure illustrates the concept of threshold dose. The threshold dose is the absorbed dose that is needed to create a clinically observed injury in the most rediosensitive individual. Example of threshold doses are given. The magnitude of these doses should be discussed. Give some example illutrating high dose rate activities in medicine e.g. Handling unshielded radioactive material etc.
  • This slide is useful to recap the concept of deterministic effects. Below a certain threshold there is no effect and beyond the threshold the effect becomes noticeable. There can be an increase in severity of the effect with dose, however, the notion of risk is not really applicable to deterministic effects.
    When discussing threshold values it is important to state the points given on the next slide.
  • The second point can be compared to drug effects
  • The diagram shows the significant increase in the frequency of leukemia among the A-bomb survivors in Hiroshima the years following the exposure,
  • Some data concerning the stochastic effects among people affected by the Chernobyl accident.
  • The diagram gives the number of thyroid cancers diagnosed in children 0-17 y the years following the Chernobyl accident. The various frequencies for the different regions is related to the exposure of the populations due to the fallout.
  • The figure should form the basis of how the risk of hereditary effects is calculated from animal experiments. E,g, select a number of groups of fruit flies and expose the groups with different absorbed dose. After a number of generations, count the number of flies that has an injury that must be a genetic defect e.g. the loss of wings. Calculate the frequency at different doses and determine the slope of this curve. This will be the risk/absorbed dose for one genetic property. The next problem is to multiply this figure with the number of genetic properties humans have. It should be the number that will lead to genetic death if they are changed. This figure is supposed to be around 30000. The slope of the dose-frequency curve is around 3*10-7 giving a risk figure for hereditary effects of about 1 %/Sv for all generations.
  • The lecturer can point out that this is animal data published in 1954
  • The figure illustrates the frequency of severe mental retardation (SMR) in different dose categories of A-bomb surviving fetus. Note the significant increase in the group 8-15 weeks gestational age.
  • Estimated threshold doses. Data are primarily based on animal experiments
  • A listing of the different groups of exposed humans used to estimate the risk of stochastic effects.
  • The first step is to determine the dose to the individuals and calculate a dose-response curve. It will generally have a sigmoid shape. The uncertainties are due to the limited number of people in each dose group. This is especially true for the heavily exposed individuals among which the majority probably died from deterministic effects.
  • The figure illustrates the concept of DDREF and the linear non threshold dose response curve.
  • The figure illustrates the different steps in the development of a fatal cancer. It should be used in a discussion of the time projection models used in calculating the risk figures.
  • This image show the difference between the two time projection models that can be used in order to estimate the radiation risk.
    Bearing in mind the long latency periods and short observation times for certain types of cancer, a model must be able to predict the future risk of a single exposure. It is now generally recognized that the multiplicative model gives the best fit to epidemiological data and it has been used by ICRP in the estimates of the probability of fatal cancer. The multiplicative model is based upon the assumption that the exposure adds an extra risk per year which increases by age at the same rate as the baseline cancer mortality range. The additive model is based upon the assumption that the exposure adds an extra risk which is constant every following year.
    The figure might be too complicated for technicians and nurses etc.
  • The risk estimates derived by the ICRP
  • The diagram illustrates the increased risk for children and young people. Discuss how this knowledge should be applied in the daily work in a nuclear medicine department e.g. the importance of having special diagnostic methods for kids and why workers <18 y are not allowed in the department.
  • <number>
    Lots of information - this slide, while self explanatory may take 3 minutes to present. If a short lecture is to be delivered it should be omitted.
  • This figure can be used in a discussion of national policies regarding termination of pregnancy due to medical exposure.
  • <number>
    NRPB (1993) Board statement on diagnostic medical exposures during pregnancy, Documents of the NRPB, 4, 1-14.
  • 01. Biological effects (7,287 KB)

    1. 1. International Atomic Energy Agency RADIATION PROTECTION IN NUCLEAR MEDICINE Part 1: Biological effects of ionizing radiation
    2. 2. Part 1. Biological effects of ionizing radiation2Nuclear Medicine OBJECTIVE To become familiar with the mechanisms of different types of biological effects following exposure to ionizing radiation and results of epidemiological studies of exposed population to ionizing radiation. To be aware of the models used to derive risk coefficients for estimating the detriment
    3. 3. Part 1. Biological effects of ionizing radiation3Nuclear Medicine CONTENT • Basic concepts, cellular effects • Deterministic effects • Stochastic effects • Effects on embryo and fetus • Risk estimates
    4. 4. International Atomic Energy Agency Part 1. Biological effects Module 1.1. Basic concepts
    5. 5. Part 1. Biological effects of ionizing radiation5Nuclear Medicine • 1895 X-rays discovered by Roentgen • 1896 First skin burns reported • 1896 First use of x-rays in the treatment of cancer • 1896 Becquerel: Discovery of radioactivity • 1897 First cases of skin damage reported • 1902 First report of x-ray induced cancer • 1911 First report of leukaemia in humans and lung cancer from occupational exposure • 1911 94 cases of tumour reported in Germany (50 being radiologists) Early Observations of the Effects of Ionizing Radiation
    6. 6. Part 1. Biological effects of ionizing radiation6Nuclear Medicine Information comes from:  studies of humans (epidemiology)  studies of animals and plants (experimental radiobiology)  fundamental studies of cells and their components (cellular and molecular biology) The key to understanding the health effects of radiation is the interaction between these sources of information. Effects of Radiation Exposure
    7. 7. Part 1. Biological effects of ionizing radiation7Nuclear Medicine Chromosomes Radiation exposure affects the centerRadiation exposure affects the center of life: the cellof life: the cell
    8. 8. Part 1. Biological effects of ionizing radiation8Nuclear Medicine
    9. 9. Part 1. Biological effects of ionizing radiation9Nuclear Medicine The critical target: DNA
    10. 10. Part 1. Biological effects of ionizing radiation10Nuclear Medicine Interaction of ionizing radiation with DNA DIRECT ACTIONDIRECT ACTION INDIRECT ACTIONINDIRECT ACTION
    11. 11. Part 1. Biological effects of ionizing radiation11Nuclear Medicine Damage to DNA
    12. 12. Part 1. Biological effects of ionizing radiation12Nuclear Medicine radiation hit cell nucleus! No change DNA mutation Exposure of the cell
    13. 13. Part 1. Biological effects of ionizing radiation13Nuclear Medicine DNA Mutation Cell survives but mutated Cancer? Cell death Mutation repaired Unviable Cell Viable Cell Outcomes after cell exposure
    14. 14. Part 1. Biological effects of ionizing radiation14Nuclear Medicine How is DNA repaired?
    15. 15. Part 1. Biological effects of ionizing radiation15Nuclear Medicine Altered base Enzyme Glycosylases recognizes lesion and releases damaged base AP-endunuclease makes incision and releases remaining sugar DNA-polymerase fills resulting gap but nick remains DNA ligase seals the nick. Repair completed. DNA has been repaired with no loss of genetic information
    16. 16. Part 1. Biological effects of ionizing radiation16Nuclear Medicine Repair The human body contains about 1014 cells. An absorbed dose of 1 mGy per year (natural sources) will produce about 1016 ionizations, which means 100 per cell in the body. If we assume that the mass of DNA is 1% of the mass of the cell, the result will be one ionization in the DNA-molecule in every cell in the body each year.
    17. 17. Part 1. Biological effects of ionizing radiation17Nuclear Medicine … order of magnitudes • 999 of 1000 lesions are repaired • 999 of 1000 damaged cells die (not a major problem as millions of cells die every day in every person) • many cells may live with damage (could be mutated)
    18. 18. Part 1. Biological effects of ionizing radiation18Nuclear Medicine Cell killing Radiosensitivity • RS = Probability of a cell, tissue or organ of suffering an effect per unit of dose. • Bergonie and Tribondeau (1906): “RS LAWS”: RS will be greater if the cell: • Is highly mitotic. • Is undifferentiated.
    19. 19. Part 1. Biological effects of ionizing radiation19Nuclear Medicine RADIOSENSITIVITY High RS Medium RS Low RS Bone Marrow Spleen Thymus Lymphatic nodes Gonads Eye lens Lymphocytes (exception to the RS laws) Skin Mesoderm organs (liver, heart, lungs…) Muscle Bones Nervous system
    20. 20. Part 1. Biological effects of ionizing radiation20Nuclear Medicine Biological effects at cellular level Possible mechanisms of cell death: • Physical death • Functional death • Death during interphase • Mitotic delay • Reproductive failure Cellular effects of ionizing radiation are studied by cell survival curves %survivalcells(semilogarithmic) Dose n = targets Dq D0 (threshold) (radiosensitivity) 100%
    21. 21. Part 1. Biological effects of ionizing radiation21Nuclear Medicine • Physical • LET (linear energy transfer): ⇑ RS • Dose rate: ⇑ RS • Temperature ⇑ RS • Chemical • Increase RS: OXYGEN, cytotoxic drugs. • Decrease RS: SULFURE (cys, cysteamine…) • Biological • Cycle status: ∀⇑ RS: G2, M ∀⇓ RS: S • Repair of damage (sub-lethal damage may be repaired e.g. fractionated dose) G1 S G2 M G0 ⇓ LET ⇑ LET %survivorcells Factors affecting radiosensitivity
    22. 22. Part 1. Biological effects of ionizing radiation22Nuclear Medicine .. ... ..... ......... .... Låg LET Hög LET low LET high LET high LET low LET Absorbed dose Surviving fraction LET (linear energy transfer) is the amount of energy (MeV) a particle will loose in traversing a certain distance (m) of a material. CELL SURVIVAL Radiation quality
    23. 23. Part 1. Biological effects of ionizing radiation23Nuclear Medicine Adapted from Marco Zaider (2000) IONIZATION PATTERN
    24. 24. Part 1. Biological effects of ionizing radiation24Nuclear Medicine Direct effects Indirect effects Cell death Primary damage Modified cell Damage to organ Somatic cells Germ cells Hereditary effects Cancer Leukemia Death of organism Repair Deterministic effects Stochastic effects BIOLOGICAL EFFECTS
    25. 25. Part 1. Biological effects of ionizing radiation25Nuclear Medicine 1 0 - 6 1 0 - 1 2 1 0 - 9 1 0 - 1 5 1 0 - 3 1 s e c o n d 1 h o u r 1 d a y 1 y e a r 1 0 0 y e a r s 1 m s 1 0 0 1 0 9 1 0 6 1 0 3 E n e r g y d e p o s itio n E x c ita tio n /io n iz a tio n In itia l p a r tic le tra c k s R a d ic a l fo r m a tio n P H Y S IC A L IN T E R A C T IO N S P H Y S IC O -C H E M IC A L IN T E R A C T IO N S B IO L O G IC A L R E S P O N S E M E D IC A L E F F E C T S D iffu s io n , c h e m ic a l r e a c tio n s In itia l D N A d a m a g e D N A b r e a k s / b a s e d a m a g e R e p a ir p r o c e s s e s D a m a g e fix a tio n C e ll k illin g P ro m o tio n /c o m p le tio n T e r a to g e n e s is C a n c e r H e r e d ita r y d e fe c ts P ro life ra tio n o f " d a m a g e d " c e lls M u ta tio n s /tra n s fo rm a tio n s /a b e rr a tio n s TIME(sec) Timing of events leading to radiation effects
    26. 26. International Atomic Energy Agency Part 1. Biological effects Module 1.2. Deterministic effects
    27. 27. Part 1. Biological effects of ionizing radiation27Nuclear Medicine EFFECTS OF CELL DEATHEFFECTS OF CELL DEATH Dose (mSv) Probability of death D 100%
    28. 28. Part 1. Biological effects of ionizing radiation28Nuclear Medicine 0 1 2 3 4 5 6 7 8 9 10 FREQUENCY ABSORBED DOSE SEVERITY Diagnostic threshold Threshold dose Most radiosensitive individual Most radioresistant individual Deterministic effects
    29. 29. Part 1. Biological effects of ionizing radiation29Nuclear Medicine • Cataracts of the lens of the eye 2-10 Gy • Permanent sterility • males 3.5-6 Gy • females 2.5-6 Gy • Temporary sterility • males 0.15 Gy • females 0.6 Gy dose Severity of effect threshold Threshold Doses for Deterministic Effects
    30. 30. Part 1. Biological effects of ionizing radiation30Nuclear Medicine Note on threshold values • Depend on dose delivery mode: • single high dose most effective • fractionation increases threshold dose in most cases significantly • decreasing the dose rate increases threshold in most cases • Threshold may differ in different persons
    31. 31. Part 1. Biological effects of ionizing radiation31Nuclear Medicine Systemic effects • Effects may be morphological and/or functional • Factors: • Which Organ • Which Dose • Effects • Immediate (usually reversible): < 6 months e.g.: inflammation, bleeding. • Delayed (usually irreversible): > 6 months e.g.: atrophy, sclerosis, fibrosis. • Criteria of dose • < 1 Gy: LOW DOSE • 1-10 Gy: MODERATE DOSE • > 10 Gy: HIGH DOSE • Regeneration means replacement by the original tissue while Repair means replacement by connective tissue.
    32. 32. Part 1. Biological effects of ionizing radiation32Nuclear Medicine Skin effects • Following the RS laws (Bergonie and Tribondeau), the most RS cells are those from the basal stratum of the epidermis. • Effects are: • Erythema: 1-24 hours after irradiation of about 3-5 Gy • Alopecia: 5 Gy is reversible; 20 Gy is irreversible. • Pigmentation: Reversible, appears 8 days after irradiation. • Dry or moist desquamation: traduces epidermal hypoplasia (dose about 20 Gy). • Delayed effects: teleangiectasia, fibrosis. DERMIS EPIDERMIS Histologic view of the skin Basal stratum cells, highly mitotic, some of them with melanin, responsible of pigmentation. From “Atlas de Histologia...”. J. Boya
    33. 33. Part 1. Biological effects of ionizing radiation33Nuclear Medicine Skin effects Injury Threshold Dose to Skin (Sv) Weeks to Onset Early transient erythema 2 <<1 Temporary epilation 3 3 Main erythema 6 1.5 Permanent epilation 7 3 Dry desquamation 10 4 Invasive fibrosis 10 Dermal atrophy 11 >14 Telangiectasis 12 >52 Moist desquamation 15 4 Late erythema 15 6-10 Dermal necrosis 18 >10 Secondary ulceration 20 >6 Skin damage from prolonged fluoroscopic exposure
    34. 34. Part 1. Biological effects of ionizing radiation34Nuclear Medicine SKIN EFFECTS By handling unshielded syringes and vials containing radioactive material the threshold dose of skin erythema will be reached in a short time. Example: The dose rate at the surface of a vial containing 30 GBq Tc99m is of the order of 2 Gy/h meaning that the threshold dose will be reached after 2 h of exposure. This corresponds to 36 s per working day in a year
    35. 35. Part 1. Biological effects of ionizing radiation35Nuclear Medicine SKIN EFFECTS Example After an extravascular injection of 500 MBq of a Tc99m radiopharmaceutical, the locally absorbed dose at the injection site might be as high as 5-20 Gy!
    36. 36. Part 1. Biological effects of ionizing radiation36Nuclear Medicine Effects in eye • Eye lens is highly RS. • Coagulation of proteins occur with doses greater than 2 Gy. • There are 2 basic effects: From “Atlas de Histologia...”. J. Boya Histologic view of eye: Eye lens is highly RS, moreover, it is surrounded by highly RS cuboid cells. > 0.155.0 Visual impairment (cataract) > 0.10.5-2.0Detectable opacities Sv/year for many years Sv single brief exposure Effect
    37. 37. Part 1. Biological effects of ionizing radiation37Nuclear Medicine Eye injuries
    38. 38. Part 1. Biological effects of ionizing radiation38Nuclear Medicine Whole body response : adult Acute irradiation syndrome Chronic irradiation syndrome Survivaltime Dose Steps: 1. Prodromic 2. Latency 3. Manifestation Lethal dose 50 / 30 BMS (bone marrow) GIS (gastro intestinal) CNS (central nervous system) 1-10 Gy 10-50 Gy > 50 Gy •Whole body clinic of a partial-body irradiation •Mechanism: Neurovegetative disorder •Similar to a sick feeling •Quite frequent in fractionated radiotherapy
    39. 39. Part 1. Biological effects of ionizing radiation39Nuclear Medicine Lethal dose 50 / 30 It is an expression of the per cent lethal dose as a function of time. It means: “Dose which would cause death to 50% of the population in 30 days”. Its value is about 2-3 Gy for humans for whole body irradiation.
    40. 40. Part 1. Biological effects of ionizing radiation40Nuclear Medicine Whole body exposure Absorbed dose (Gy) Syndrome or tissue involved Symptoms 1-10 Bone marrow syndrome Leucopenia, thrombopenia, hemorrhage, infections 10-50 Gastrointestinal Diarrhoea, fever, electrolytic imbalance >50 Central nervous syndrome Cramps, tremor, ataxia, lethargy, impaired vision, coma
    41. 41. Part 1. Biological effects of ionizing radiation41Nuclear Medicine Whole body exposure Absorbed dose (Gy) Therapy Prognosis 1-10 Symptomatic Transfusions of leucocytes and platelets. Bone marrow transplantation Growth stimu- lating factors Excellent to uncertain 10-50 Palliative Very poor >50 Symptomatic Hopeless Lethality 0-90% 90-100% 100%
    42. 42. International Atomic Energy Agency Part 1. Biological effects Module 1.3. Stochastic effects
    43. 43. Part 1. Biological effects of ionizing radiation43Nuclear Medicine STOCHASTIC EFFECTS OF IONIZING RADIATION
    44. 44. Part 1. Biological effects of ionizing radiation44Nuclear Medicine STOCHASTIC EFFECTS OF IONIZING RADIATION Health consequences of Chernobyl accident •1800 children diagnosed with thyroid cancer (1998)
    45. 45. Part 1. Biological effects of ionizing radiation45Nuclear Medicine STOCHASTIC EFFECTS OF IONIZING RADIATION Thyroid cancer diagnosed up to 1998 among children 0-17 years at the time of the Chernobyl accident 0 50 100 150 200 250 300 1990 1991 1992 1993 1994 1995 1996 1997 1998 Year Number Belarus Russian Federation Ukraine Total
    46. 46. Part 1. Biological effects of ionizing radiation46Nuclear Medicine Frequency (%) 10 20 30 40 Absorbed dose (Gy) 10 5 0 Genetic effects
    47. 47. Part 1. Biological effects of ionizing radiation47Nuclear Medicine Genetic Effects • Ionising radiation is known to cause heritable mutations in many plants and animals BUT • intensive studies of 70,000 offspring of the atomic bomb survivors have failed to identify an increase in congenital anomalies, cancer, chromosome aberrations in circulating lymphocytes or mutational blood protein changes. Neel et al. Am. J. Hum. Genet. 1990, 46:1053-1072Neel et al. Am. J. Hum. Genet. 1990, 46:1053-1072
    48. 48. International Atomic Energy Agency Part 1. Biological effects Module 1.4. Effects on embryo and fetus
    49. 49. Part 1. Biological effects of ionizing radiation49Nuclear Medicine Sensitivity of the early conceptus • Till early 1980’s, early conceptus was considered to be very sensitive to radiation - although no one knew how sensitive? • Realization that: • organogenesis starts 3-5 weeks after conception • In the period before organogenesis high radiation exposure may lead to failure to implant. Low dose may not have any observable effect.
    50. 50. Part 1. Biological effects of ionizing radiation50Nuclear Medicine Incidence of Prenatal & Neonatal Death and Abnormalities Hall, Radiobiology for the Radiologist pg 365
    51. 51. Part 1. Biological effects of ionizing radiation51Nuclear Medicine PRE-IMPLANTATION
    52. 52. Part 1. Biological effects of ionizing radiation52Nuclear Medicine Pre-implant stage (up to 10 days)  Only lethal effect, all or none  Embryo contains only few cells which are not specialized  If too many cell are damaged-embryo is resorbed  If only few killed-remaining pluripotent cells replace the cells loss within few cell divisions  Atomic Bomb survivors - high incidence of both - normal birth and spontaneous abortion
    53. 53. Part 1. Biological effects of ionizing radiation53Nuclear Medicine
    54. 54. Part 1. Biological effects of ionizing radiation54Nuclear Medicine Fetal Radiation Risk • There are radiation-related risks throughout pregnancy which are related to the stage of pregnancy and absorbed dose • Radiation risks are most significant during organogenesis and in the early fetal period somewhat less in the 2nd trimester and least in the third trimester Less Least Most risk
    55. 55. Part 1. Biological effects of ionizing radiation55Nuclear Medicine Radiation-Induced Malformations • Malformations have a threshold of 100-200 mGy or higher and are typically associated with central nervous system problems • Fetal doses of 100 mGy are not reached even with 3 pelvic CT scans or 20 conventional diagnostic x-ray examinations • These levels can be reached with fluoroscopically guided interventional procedures of the pelvis and with radiotherapy
    56. 56. Part 1. Biological effects of ionizing radiation56Nuclear Medicine Central Nervous System Effects • During 8-25 weeks post-conception the CNS is particularly sensitive to radiation • Fetal doses in excess of 100 mGy can result in some reduction of IQ (intelligence quotient) • Fetal doses in the range of 1000 mGy can result in severe mental retardation particularly during 8-15 weeks and to a lesser extent at 16-25 weeks
    57. 57. Part 1. Biological effects of ionizing radiation57Nuclear Medicine Heterotopic gray matter (arrows) near the ventricles in a mentally retarded individual occurring as a result of high dose in-utero radiation exposure
    58. 58. Part 1. Biological effects of ionizing radiation58Nuclear Medicine Effects on embryo and fetus
    59. 59. Part 1. Biological effects of ionizing radiation59Nuclear Medicine Age Threshold for lethal effects (mGy) Threshold for malformations (mGy) 1 day 100 No effect 14 days 250 - 18 days 500 250 20 days >500 250 50 days >1000 500 50 days to birth >1000 >500 Effects on embryo and fetus
    60. 60. Part 1. Biological effects of ionizing radiation60Nuclear Medicine Leukemia and Cancer • Radiation has been shown to increase the risk for leukemia and many types of cancer in adults and children • Throughout most of pregnancy, the embryo/fetus is assumed to be at about the same risk for carcinogenic effects as children
    61. 61. Part 1. Biological effects of ionizing radiation61Nuclear Medicine Leukemia and Cancer • The relative risk may be as high as 1.4 (40% increase over normal incidence) due to a fetal dose of 10 mGy • Individual risk, however, is small with the risk of cancer at ages 0-15 being about 1 excess cancer death per 1,700 children exposed “in utero” to 10 mGy
    62. 62. International Atomic Energy Agency Part 1. Biological effects Module 1.5. Risk estimates
    63. 63. Part 1. Biological effects of ionizing radiation63Nuclear Medicine Risk Estimates • Risk = probability of effect • Different effects can be looked at - one needs to carefully look at what effect is considered: E.g. Thyroid cancer mortality is NOT identical to thyroid cancer incidence!!!! • Risk estimates usually obtained from high doses and extrapolated to low doses
    64. 64. Part 1. Biological effects of ionizing radiation64Nuclear Medicine EPIDEMIOLOGICAL DATA FROM: Hiroshima-Nagasaki Patients with ancylosing spondylitis cervical cancer tuberculosis mastitis tinea capitis thymus enlargement thyrotoxicosis hemangiomas and more may come Chernobyl Techa river Semiplatinsk Nevada ……..
    65. 65. Part 1. Biological effects of ionizing radiation65Nuclear Medicine Populations used in the UNSCEAR Reports Characteristic Atomic Bomb Survivors Spondylitis Series Cervical Cancer Series Number 86,500 14,000 83,000 Age at irradiation 0 -> 90 > 15 < 30 -> 70 Average follow-up 28.8 y 23.0 y 7.6 y Mean dose 0.24 Gy 1.9 Gy Inhomogeneous Range of doses 0.01 – 6.0 Gy 0 – 8.06 Gy Type of irradiation Instantaneous / whole-body Fractionated / partial-body Chronic / partial-body
    66. 66. Part 1. Biological effects of ionizing radiation66Nuclear Medicine How to use epidemiological data to estimate radiation risks at low doses?
    67. 67. Part 1. Biological effects of ionizing radiation67Nuclear Medicine Dose-response curve Frequency of leukemia (cases/1 miljon) Equivalent dose (mSv)
    68. 68. Part 1. Biological effects of ionizing radiation68Nuclear Medicine Mortality of the Atomic Bomb Survivors Dose response curve for Solid Cancer • The dose response is linear up to about 3 Sv with a slope of 0.37 ERR/Sv • The excess lifetime risk per Sv for those exposed at age 30 is estimated at 0.10 and 0.14 for males and females respectively • The “lowest dose at which there is a statistically significant excess risk” is shown to be 50 mSv Pierce DA et al, Rad Res 1996; 146:1-27Pierce DA et al, Rad Res 1996; 146:1-27
    69. 69. Part 1. Biological effects of ionizing radiation69Nuclear Medicine Latest news from the Hiroshima-Nagasaki cohort Extra years 1986-1990 There are now 10 500 survivors with DS86-dosimetry out of a total population of 86 572, who were irradiated 44% had died by the end of 1990. The data is incomplete in that deaths in the first five years are not included. 7 827 have died from cancer, there being 420 excess cancer deaths. 1945-1950 1950-90 (1986-90) Leukemia ? 87 (3) Solid cancer ? 335 (88) ------------------------------------------------------------------- 420 Risk for children/Risk for adults = 1.4 - 1.7
    70. 70. Part 1. Biological effects of ionizing radiation70Nuclear Medicine RADIATION RISKS 0 1 2 3 4 5 6 7 8 9 10 ABSORBED DOSE PROBABILITYOFFATALCANCER Observations Deterministic effects Linear-quadratic model
    71. 71. Part 1. Biological effects of ionizing radiation71Nuclear Medicine What happens at the low-dose end of the graph? a) Linear extrapolation b) Threshold dose c) Lower risk per dose for low doses d) Higher risk per dose for for low doses
    72. 72. Part 1. Biological effects of ionizing radiation72Nuclear Medicine Low doses: <0.2 Gy(Sv) Low dose rates: < 0.1 Gy(Sv)/hour (ICRP) 0.1 Gy(Sv)/day (NCRP) P = A*D + B*D2 P is the probability of cancer induction The quotient A/B is called DDREF (Dose and Dose Rate Effectiveness Factor) and has been assigned by ICRP the value 2 for low LET radiation, low doses and low dose rates.
    73. 73. Part 1. Biological effects of ionizing radiation73Nuclear Medicine Epidemiological Evidence 1 10 100 1000 10000 0.1 1 10 100 1000 10000 Dose (mGy) Cancerdeaths/year/1Mpeople natural cancer mortality additional cancer deaths due to radiation Linear No-Threshold (LNT) Hypothesis reduced at low dose and dose rate by a factor of 2 - in general agreement with data
    74. 74. Part 1. Biological effects of ionizing radiation74Nuclear Medicine CANCER initiation pre-cancer stage promotion growth detection metastasis Elimination and repair latency period period of suffering death lifetime loss
    75. 75. Part 1. Biological effects of ionizing radiation75Nuclear Medicine Carcinogenic Effects An assessment of the atomic bomb survivors showed: • the leukaemia risk peaked at 10 years after exposure • thyroid cancer was the first solid cancer reported • the incidence of breast cancer was higher in young women than older women • other cancer, with a latent period of up to 30 years, included lung, stomach, colon, bladder and oesophagus Shimizu et al JAMA 1990, 264:601-604Shimizu et al JAMA 1990, 264:601-604
    76. 76. Part 1. Biological effects of ionizing radiation76Nuclear Medicine Variation of Cancer Incidence with time following the Atomic Bombs
    77. 77. Part 1. Biological effects of ionizing radiation77Nuclear Medicine Variation of CancerVariation of Cancer Incidence with timeIncidence with time following thefollowing the Atomic BombsAtomic Bombs
    78. 78. Part 1. Biological effects of ionizing radiation78Nuclear Medicine ICRP 60 Time projection models Lifetime Expression, Comparison of Absolute and Relative Risk Models Absolute Risk Relative Risk Incidence Incidence 0 xo xo+l 90 0 xo xo+l 90 Incidence after irradiation Spontaneous incidence
    79. 79. Part 1. Biological effects of ionizing radiation79Nuclear Medicine RADIATION RISKS Effect Population Exposure period Probability Hereditary effects Whole population Lifetime 1 %/Sv (all generations) Fatal cancer Whole population Lifetime 5 %/Sv Fatal cancer Working population Age 18-65 4 %/Sv Health detriment Whole population Lifetime 7.3 %/Sv Health detriment Working population Age 18-65 5.6 %/Sv
    80. 80. Part 1. Biological effects of ionizing radiation80Nuclear Medicine 0 10 20 30 40 50 60 70 80 (age at exposure) 20 15 10 5 0 Male Female Risk (%/ Sv) for Cancer induction by Age at exposure and Sex
    81. 81. Part 1. Biological effects of ionizing radiation81Nuclear Medicine UNSCEAR has recently (2000) further assessed the cancer risk from radiation exposures. For a population of all ages and both genders, the life- time risk of dying from radiation induced cancer after an acute dose of 1000 mSv is about 9% for men and 13% for women or 11% as a mean. Applying a DDREF of 2, these data confirm the 10 years old ICRP estimate. Life-time risk of dying from radiation induced cancer = 5% per sievert
    82. 82. Part 1. Biological effects of ionizing radiation82Nuclear Medicine In the latest Hiroshima-Nagasaki Life Span Study (1986- 1990), LSS Report 12, (Pierce et al., 1996) find the nominal estimates of risk (5% per Sv) to apply down to a dose of about 50 mSv. For childhood cancer following fetal irradiation, very similar risk estimates (6% per Sv) are found to apply to doses of 10 mSv (Doll and Wakeford, 1997). The risk estimates and the uncertainties associated with them are expected to apply at low doses. EFFECTS AT LOW DOSES
    83. 83. Part 1. Biological effects of ionizing radiation83Nuclear Medicine NCRP, 1997 Probability distribution of lifetime risk coefficient. The 90% confidence interval is shown by the arrows (5% should be read as 1% - 9%). Uncertainties in fatal cancer risk estimate (5% per Sv) Lifetime Risk Coefficient (%/Sv) 0.00 1.20 2.75 5.50 8.25 8.84 11.0 0.000 0.007 0.013 0.020 0.027 Frequency chart 100 000 Trials Shown Probability
    84. 84. Part 1. Biological effects of ionizing radiation84Nuclear Medicine Sensitivity chart of uncertainty component influence (population of all ages) From NCRP, 1997 Uncertainties in fatal cancer risk estimates
    85. 85. Part 1. Biological effects of ionizing radiation85Nuclear Medicine Threshold dose deterministic effects 50-100 mSv Mental retardation 40% / Sv Cancer and leukemia before 10 y of age 2% / Sv lifetime 15% / Sv Hereditary effects 1% / Sv Radiation risks - embryo and fetus
    86. 86. Part 1. Biological effects of ionizing radiation86Nuclear Medicine Time after Effect Normal incidence conception in live-born First three weeks No deterministic or stochastic - effects in live-born child 3rd through 8th Potential for malformation of 0.06 weeks organsa (1 in 17) 8th through 25th Potential for severe mental 5 x 10-3 weeks retardationb (1 in 200) 4th week throughout Cancer in childhood or in adult 1 x 10-3 pregnancy lifec (1 in 1000) a Deterministic effect. Threshold ~ 0.1 Gy b 30 IQ units shift: 8-15th week; <30 IQ units shift: 16 - 25th week c Risk in utero ~ risk < 10 years of age TYPES OF EFFECTS FOLLOWING IRRADIATION IN UTERO
    87. 87. Part 1. Biological effects of ionizing radiation87Nuclear Medicine Radiation risks embryo and fetus Dose (mGy) Lethal effects malformations Mental retardation Cancer & leukemia before 10 years Cancer & leukemia whole life 1 none -> 1*10-4 4*10-4 5*10-5 1.5*10-4 10 none -> 1*10-3 4*10-3 5*10-4 1.5*10-3 50 none -> 5*10-3 2*10-2 2.5*10-3 7.5*10-3 100 none -> 1*10-2 4*10-2 5*10-3 1.5*10-2 Other reasons 3*10-3 4*10-2 7*10-3 1*10-3 0.2 Data from Sweden 1992
    88. 88. Part 1. Biological effects of ionizing radiation88Nuclear Medicine Risks in a pregnant population not exposed to medical radiation • Spontaneous abortion > 15% • incidence of genetic abnormalities 4- 10% • intrauterine growth retardation 4% • incidence of major malformation 2- 4%
    89. 89. Part 1. Biological effects of ionizing radiation89Nuclear Medicine Probability of bearing healthy children as a function of radiation dose Dose to conceptus (mGy) above natural background Probability of no malformation Probability of no cancer (0-19 years) 0 97 99.7 1 97 99.7 5 97 99.7 10 97 99.6 50 97 99.4 100 97 99.1 >100 possible, see text higher
    90. 90. Part 1. Biological effects of ionizing radiation90Nuclear Medicine Approximate fetal whole body dose (mGy) from common nuclear medicine procedures done in early and late pregnancy Procedure Activity (MBq) Early 9 months Tc-99m Bone scan Lung V/Q scan Liver colloid Thyroid scan Renal DTPA Red Cell 750 240 300 400 750 930 4.7 0.9 0.6 4.4 9.0 6.0 1.8 0.9 1.1 3.7 3.5 2.5 I-123 thyroid uptake 30 0.6 0.3 I-131 thyroid uptake 0.55 0.04 0.15
    91. 91. Part 1. Biological effects of ionizing radiation91Nuclear Medicine Doses and Risks for in Utero Radiodiagnostics Exposure Mean foetal dose Hered. Disease Fatal cancer (mGy) to age 14 y X-ray Abdomen 2.6 6.2 10-5 7.7 10-5 Barium enema 16 3.9 10-4 4.8 10-4 Barium meal 2.8 6.7 10-5 8.4 10-5 IV urography 3.2 7.7 10-5 9.6 10-5 Lumbar spine 3.2 7.6 10-5 9.5 10-5 Pelvis 1.7 4.0 10-5 5.1 10-5 Computed tomography Abdomen 8.0 1.9 10-4 2.4 10-4 Lumbar spine 2.4 5.7 10-5 7.1 10-5 Pelvis 25 6.1 10-4 7.7 10-4 Nuclear medicine Tc bone scan 3.3 7.9 10-4 1.0 10-4 Tc brain scan 4.3 1.0 10-5 1.3 10-4
    92. 92. Part 1. Biological effects of ionizing radiation92Nuclear Medicine Comment on Fetus/Embryo • Fetus/embryo is more sensitive to ionizing radiation than the adult human • Increased incidence of spontaneous abortion a few days after conception • Increased incidence • Mental retardation • Microcephaly (small head size) especially 8-15 weeks after conception • Malformations: skeletal, stunted growth, genital • Higher risk of cancer (esp. leukemia) • Both in childhood and later life
    93. 93. Part 1. Biological effects of ionizing radiation93Nuclear Medicine Scale of Radiation Exposures 1 10 100 1000 10000 0.1 1 10 100 1000 10000 Dose (mGy) Cancerdeaths/year/1Mpeople natural cancer mortality additional cancer deaths due to radiation Annual Background CT scan Bone scan Typical Radiotherapy Fraction
    94. 94. Part 1. Biological effects of ionizing radiation94Nuclear Medicine Example for Risk Calculation • Assume • Risk of 0.05 per Sv • 1,000 people are exposed to 5 mSv/y for 20 y • Expected additional cancer deaths is 0.05 [cancers/Sv]x0.005[Sv/y]x20[y]x1,000[people] = 5 additional cancer deaths due to radiation (5/1000) • General population: 23% (230/1000) of all deaths due to cancer (difficult to ascertain 5 additional ones caused by radiation) • Calculations become more complex for individual tissue exposures vs. whole body exposures
    95. 95. Part 1. Biological effects of ionizing radiation95Nuclear Medicine Examination Skin dose Effective dose Risk (mGy) (mGy) (%) Urography 30 8 0.04 Lumbar spine 40 5 0.025 Abdomen 10 2.5 0.013 Chest 2 0.25 0.0013 Extremities 3 0.025 0.00013 RADIATION RISKS IN X-RAY EXAMINATIONS
    96. 96. Part 1. Biological effects of ionizing radiation96Nuclear Medicine Examination Radiopharmaceutical Effective dose Risk (mSv) (%) Myocardium Tl-201 chloride 23 0.12 Bone Tc-99m MDP 3.6 0.018 Thyroid Tc-99m pertechnetate 1.1 0.006 Lungs Tc-99m MAA 0.9 0.005 Kidney clearance Cr-51 EDTA 0.01 0.00005 RADIATION RISKS IN NUCLEAR MEDICINE
    97. 97. Part 1. Biological effects of ionizing radiation97Nuclear Medicine Average Annual Risk of Death in the UK from Industrial Accidents and from Cancers due to Radiation Work Coal mining 1 in 7,000 Oil and gas extraction 1 in 8,000 Construction 1 in 16,000 Radiation work (1.5 mSv/y) 1 in 17,000 Metal manufacture 1 in 34,000 All manufacture 1 in 90,000 Chemical production 1 in 100,000 All services 1 in 220,000 From L Collins 2000 These figures can be compared to an estimate of 1 in 17000 for 1.5 mSv/year received by radiation workers
    98. 98. Part 1. Biological effects of ionizing radiation98Nuclear Medicine Comparison of Radiation Worker Risks to Other Workers Mean death rate 1989 (10-6 /y) Trade 40 Manufacture 60 Service 40 Government 90 Transport/utilities 240 Construction 320 Agriculture 400 Mines/quarries 430 Safe industries ≡ 2 mSv/y (100 mSv over a lifetime) ≡ max permissible exposuremax permissible exposure (20 mSv/year or 1000 mSv(20 mSv/year or 1000 mSv over a lifetimeover a lifetime
    99. 99. Part 1. Biological effects of ionizing radiation99Nuclear Medicine The following activities are associated with a risk of death that is 1/1000000 •10 days work in a nuclear medicine department • smoking 1.4 cigarette • living 2 days in a polluted city • traveling 6 min in a canoe • 1.5 min mountaineering • traveling 480 km in a car • traveling 1600 km in an airplane • living 2 months together with a smoker • drinking 30 cans of diet soda RISKS
    100. 100. Part 1. Biological effects of ionizing radiation100Nuclear Medicine Expected reduction of life Unmarried man 3500 days Smoking man 2250 days Unmarried woman 1600 days 30% overweight 1300 days Cancer 980 days Construction work 300 days Car accident 207 days Accident at home 95 days Administrative work 30 days Radiological examination 6 days RISKS
    101. 101. Part 1. Biological effects of ionizing radiation101Nuclear Medicine Questions??
    102. 102. Part 1. Biological effects of ionizing radiation102Nuclear Medicine DISCUSSION A woman was referred to a bone scan. After the examination she turned out to be pregnant at a very early stage. She is extremely worried and wants to have an abortion. Discuss how to act.
    103. 103. Part 1. Biological effects of ionizing radiation103Nuclear Medicine DISCUSSION Dose fractionation results in: • increased radiation sensitivity for photons? • decreased radiation sensitivity for photons? • decreased radiation sensitivity for heavy charged particles? • increased radiation sensitivity for heavy charged particles?
    104. 104. Part 1. Biological effects of ionizing radiation104Nuclear Medicine DISCUSSION A patient (radiobiologist) wants to know the radiation risk he will suffer in an examination of the cerebral blood flow (1000 MBq 99m Tc). What to answer?
    105. 105. Part 1. Biological effects of ionizing radiation105Nuclear Medicine Where to Get More Information • Other sessions • Part 2 Radiation Physics • Further readings • WHO/IAEA. Manual on Radiation Protection in Hospital and General Practice. Volume 1. Basic requirements (draft manuscript) • ICRP publications (41, 60, 84) • UNSCEAR reports • ALPEN E.L Radiation Biophysics. Academic Press, 1998 • RUSSEL, J.G.B., Diagnostic radiation, pregnancy and termination, Br. J. Radiol. 62 733 (1989) 92-3.

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