RADIATION PROTECTION IN NUCLEAR MEDICINE

RADIATION PROTECTION IN NUCLEAR MEDICINE
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine RADIATION PROTECTION IN NUCLEAR MEDICINE Part 1: Biological Effects of Ionizing Radiation

Part 1. Biological effects of ionizing radiation
Objective Radiation Protection in Nuclear Medicine 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 Part 1. Biological effects of ionizing radiation

Contents Radiation Protection in Nuclear Medicine Basic concepts, cellular effects Deterministic effects Stochastic effects Effects on embryo and fetus Risk estimates Part 1. Biological effects of ionizing radiation

Part 1. Biological Effects
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Part 1. Biological Effects Module 1.1. Basic Concepts

Early Observations of the Effects of Ionizing Radiation
Part 1. Biological effects of ionizing radiation Early Observations of the Effects of Ionizing Radiation Radiation Protection in Nuclear Medicine X-rays discovered by Roentgen First skin burns reported First use of x-rays in the treatment of cancer Becquerel: Discovery of radioactivity First cases of skin damage reported First report of x-ray induced cancer First report of leukaemia in humans and lung cancer from occupational exposure cases of tumour reported in Germany (50 being radiologists) Part 1. Biological effects of ionizing radiation

Effects of Radiation Exposure
Part 1. Biological effects of ionizing radiation Effects of Radiation Exposure Radiation Protection in Nuclear 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. Part 1. Biological effects of ionizing radiation

Radiation exposure affects the center of life: the cell Chromosomes Part 1. Biological effects of ionizing radiation

The critical target: DNA
Part 1. Biological effects of ionizing radiation

Interaction of ionizing radiation with DNA
DIRECT ACTION INDIRECT ACTION Part 1. Biological effects of ionizing radiation

Damage to DNA Part 1. Biological effects of ionizing radiation

radiation hit cell nucleus!
Exposure of the Cell No change radiation hit cell nucleus! DNA mutation Part 1. Biological effects of ionizing radiation

Outcomes after cell exposure
Viable Cell Mutation repaired Unviable Cell Cell death Cancer? DNA Mutation Cell survives but mutated Part 1. Biological effects of ionizing radiation

How is DNA repaired? Part 1. Biological effects of ionizing radiation

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 Part 1. Biological effects of ionizing radiation

Repair Radiation Protection in Nuclear Medicine The human body contains about 1014 cells. An absorbed dose of 1 mGy per year (natural sources) will produce about 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. 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. Part 1. Biological effects of ionizing radiation

… order of magnitudes Radiation Protection in Nuclear Medicine 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) 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. Part 1. Biological effects of ionizing radiation

Cell killing Radiosensitivity
Part 1. Biological effects of ionizing radiation Cell killing Radiosensitivity Radiation Protection in Nuclear Medicine 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. Part 1. Biological effects of ionizing radiation

RADIOSENSITIVITY Radiation Protection in Nuclear Medicine 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 Part 1. Biological effects of ionizing radiation

Biological Effects at Cellular Level
Part 1. Biological effects of ionizing radiation Biological Effects at Cellular Level Radiation Protection in Nuclear Medicine 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 n = targets Exponential % survival cells (semi logarithmic) 100% Dq (threshold) D0 (radiosensitivity) Dose Part 1. Biological effects of ionizing radiation

Factors Affecting Radiosensitivity
Part 1. Biological effects of ionizing radiation Factors Affecting Radiosensitivity Radiation Protection in Nuclear 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) % survivor cells  LET  LET G0 M G2 G1 S Part 1. Biological effects of ionizing radiation

Cell Survival Radiation Quality
Part 1. Biological effects of ionizing radiation Cell Survival Radiation Quality Radiation Protection in Nuclear Medicine low LET Surviving fraction low LET high LET high LET Absorbed dose LET (linear energy transfer) is the amount of energy (MeV) a particle will loose in traversing a certain distance (m) of a material. Part 1. Biological effects of ionizing radiation

Ionization Pattern Radiation Protection in Nuclear Medicine 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 Adapted from Marco Zaider (2000) Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear Medicine Direct effects Indirect effects Repair Primary damage Cell death Modified cell Damage to organ Somatic cells Germ cells 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. Death of organism Cancer Leukemia Hereditary effects Deterministic effects Stochastic effects Part 1. Biological effects of ionizing radiation

Timing of Events leading to Radiation Effects
Part 1. Biological effects of ionizing radiation

Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Part 1. Biological Effects Module 1.2. Deterministic Effects

Effects of Cell Death Probability of death 100% Dose (mSv) D Part 1. Biological effects of ionizing radiation

Deterministic Effects
Part 1. Biological effects of ionizing radiation Deterministic Effects Radiation Protection in Nuclear Medicine SEVERITY Most radiosensitive Most radioresistant individual individual Diagnostic threshold FREQUENCY 1 2 3 4 5 6 7 8 9 10 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. Threshold ABSORBED DOSE dose Part 1. Biological effects of ionizing radiation

Threshold Doses for Deterministic Effects
Part 1. Biological effects of ionizing radiation Threshold Doses for Deterministic Effects Radiation Protection in Nuclear Medicine Cataracts of the lens of the eye Gy [ICRP statement on tissue reactions ( nt%20on%20tissue%20reactions.pdf)] Permanent sterility males Gy females Gy Temporary sterility males Gy females Gy dose Severity of effect threshold 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. Part 1. Biological effects of ionizing radiation

Note on Threshold Values
Part 1. Biological effects of ionizing radiation Note on Threshold Values Radiation Protection in Nuclear Medicine 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 The second point can be compared to drug effects Part 1. Biological effects of ionizing radiation

Systemic Effects Radiation Protection in Nuclear Medicine 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. Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear 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. Histologic view of the skin DERMIS EPIDERMIS From “Atlas de Histologia...”. J. Boya Basal stratum cells, highly mitotic, some of them with melanin, responsible of pigmentation. Part 1. Biological effects of ionizing radiation

Skin Effects Skin damage from prolonged fluoroscopic exposure Part 1. Biological effects of ionizing radiation

Skin Effects Radiation Protection in Nuclear Medicine 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 Part 1. Biological effects of ionizing radiation

Skin Effects Radiation Protection in Nuclear Medicine 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! Part 1. Biological effects of ionizing radiation

Effects in Eye Radiation Protection in Nuclear Medicine Eye lens is highly RS. Coagulation of proteins occurs with doses greater than 2 Gy. There are 2 basic effects: Histologic view of eye: Effect Sv single brief exposure Sv/year for many years Detectable opacities > 0.1 Visual impairment (cataract) 5.0 > 0.15 From “Atlas de Histologia...”. J. Boya Eye lens is highly RS, moreover, it is surrounded by highly RS cuboid cells. The ICRP has stated in 2011 that the threshold for tissue reactions in lens of the eye is 0.5 Gy. Part 1. Biological effects of ionizing radiation

Eye Injuries Radiation Protection in Nuclear Medicine Part 1. Biological effects of ionizing radiation

Whole Body Response : Adult
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine 1 2 Chronic irradiation syndrome Acute irradiation syndrome 1-10 Gy Steps: Prodromic Latency Manifestation Whole body clinic of a partial-body irradiation Mechanism: Neurovegetative disorder Similar to a sick feeling Quite frequent in fractionated radiotherapy 10-50 Gy > 50 Gy Survival time BMS (bone marrow) GIS (gastro intestinal) Lethal dose 50 / 30 CNS (central nervous system) Dose Part 1. Biological effects of ionizing radiation

Lethal Dose 50/30 Radiation Protection in Nuclear Medicine 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. Part 1. Biological effects of ionizing radiation

Whole Body Exposure Radiation Protection in Nuclear Medicine 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 Part 1. Biological effects of ionizing radiation

Whole Body Exposure Radiation Protection in Nuclear Medicine Absorbed dose (Gy) Therapy Prognosis 1-10 Symptomatic Transfusions of leucocytes and platelets. Bone marrow transplantationGrowth stimu-lating factors Excellent to uncertain 10-50 Palliative Very poor >50 Symptomatic Hopeless Lethality 0-90% 90-100% 100% Part 1. Biological effects of ionizing radiation

Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Part 1. Biological Effects Module 1.3. Stochastic Effects

Stochatic Effects of Ionizing Radiation
Part 1. Biological effects of ionizing radiation Stochatic Effects of Ionizing Radiation Radiation Protection in Nuclear Medicine The diagram shows the significant increase in the frequency of leukemia among the A-bomb survivors in Hiroshima the years following the exposure, Part 1. Biological effects of ionizing radiation

Part 1. Biological effects of ionizing radiation Stochatic Effects of Ionizing Radiation Radiation Protection in Nuclear Medicine Health consequences of Chernobyl accident 1800 children diagnosed with thyroid cancer (1998) Some data concerning the stochastic effects among people affected by the Chernobyl accident. Part 1. Biological effects of ionizing radiation

Part 1. Biological effects of ionizing radiation Stochatic Effects of Ionizing Radiation Radiation Protection in Nuclear Medicine 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. Part 1. Biological effects of ionizing radiation

Genetic Effects Radiation Protection in Nuclear Medicine Frequency (%) 10 5 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 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. Absorbed dose (Gy) Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear Medicine Genetic Effects Ionizing 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 , 46: Part 1. Biological effects of ionizing radiation

Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Part 1. Biological Effects Module 1.4. Effects on Embryo and Fetus

Sensitivity of the Early Conceptus
Part 1. Biological effects of ionizing radiation Sensitivity of the Early Conceptus Radiation Protection in Nuclear Medicine 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. Part 1. Biological effects of ionizing radiation

Incidence of Prenatal & Neonatal Death and Abnormalities
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Incidence of Prenatal & Neonatal Death and Abnormalities The lecturer can point out that this is animal data published in 1954 Hall, Radiobiology for the Radiologist pg 365 Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear Medicine Pre-Implantation Part 1. Biological effects of ionizing radiation

Pre-Implant Stage (up to 10 days)
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear 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 Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear Medicine Part 1. Biological effects of ionizing radiation

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 Most risk Less Least Part 1. Biological effects of ionizing radiation

Radiation-Induced Malformations
Malformations have a threshold of 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 Part 1. Biological effects of ionizing radiation

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 weeks Part 1. Biological effects of ionizing radiation

Heterotopic gray matter (arrows) near the ventricles in a mentally retarded individual occurring as a result of high dose in-utero radiation exposure Part 1. Biological effects of ionizing radiation

Effects on Embryo and Fetus
Part 1. Biological effects of ionizing radiation Effects on Embryo and Fetus Radiation Protection in Nuclear Medicine 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. Part 1. Biological effects of ionizing radiation

Effects on Embryo and Fetus
Part 1. Biological effects of ionizing radiation Effects on Embryo and Fetus Radiation Protection in Nuclear Medicine Age Threshold for lethal effects (mGy) Threshold for malformations (mGy) 1 day 100 No effect 14 days 250 - 18 days 500 20 days >500 50 days >1000 50 days to birth Estimated threshold doses. Data are primarily based on animal experiments Part 1. Biological effects of ionizing radiation

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 Part 1. Biological effects of ionizing radiation

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 Part 1. Biological effects of ionizing radiation

Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Part 1. Biological Effects Module 1.5. Risk Estimates

Radiation Protection in Nuclear 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 Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear Medicine Epidemiological Data: 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 …….. A listing of the different groups of exposed humans used to estimate the risk of stochastic effects. Part 1. Biological effects of ionizing radiation

Populations used in the UNSCEAR Reports
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Populations used in the UNSCEAR Reports Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear Medicine How to Use Epidemiological Data to Estimate Radiation Risks at Low Doses? Part 1. Biological effects of ionizing radiation

Dose-Response Curve Radiation Protection in Nuclear Medicine Frequency of leukemia (cases/1 miljon) 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. Equivalent dose (mSv) Part 1. Biological effects of ionizing radiation

Mortality of the Atomic Bomb Survivors
Part 1. Biological effects of ionizing radiation Mortality of the Atomic Bomb Survivors Radiation Protection in Nuclear Medicine 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; 146:1-27 Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear Medicine Latest news from the Hiroshima-Nagasaki Cohort Extra years There are now survivors with DS86-dosimetry out of a total population of , who were irradiated 44% had died by the end of The data is incomplete in that deaths in the first five years are not included have died from cancer, there being 420 excess cancer deaths ( ) Leukemia ? (3) Solid cancer ? (88) Risk for children/Risk for adults = Part 1. Biological effects of ionizing radiation

Radiation Risks Radiation Protection in Nuclear Medicine Linear-Quadratic Model Part 1. Biological effects of ionizing radiation

What happens at the low-dose end of the graph?
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine What happens at the low-dose end of the graph? Linear extrapolation Threshold dose Lower risk per dose for low doses Higher risk per dose for for low doses Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear Medicine 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. The figure illustrates the concept of DDREF and the linear non threshold dose response curve. Low doses: <0.2 Gy(Sv) Low dose rates: < 0.1 Gy(Sv)/hour (ICRP) 0.1 Gy(Sv)/day (NCRP) Part 1. Biological effects of ionizing radiation

Epidemiological Evidence
Part 1. Biological effects of ionizing radiation Epidemiological Evidence Radiation Protection in Nuclear Medicine Linear No-Threshold (LNT) Hypothesis reduced at low dose and dose rate by a factor of 2 - in general agreement with data Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear Medicine Cancer initiation pre-cancer stage promotion growth detection metastasis Elimination and repair latency period period of suffering death lifetime loss 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. Part 1. Biological effects of ionizing radiation

Carcinogenic Effects Radiation Protection in Nuclear Medicine 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: Part 1. Biological effects of ionizing radiation

Variation of Cancer Incidence with time following the Atomic Bombs
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Variation of Cancer Incidence with time following the Atomic Bombs Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear Medicine Variation of Cancer Incidence with time following the Atomic Bombs Part 1. Biological effects of ionizing radiation

Time Projection Models
Part 1. Biological effects of ionizing radiation Time Projection Models Radiation Protection in Nuclear Medicine Lifetime Expression, Comparison of Absolute and Relative Risk Models Incidence Incidence Absolute Risk Relative Risk Incidence after irradiation 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. Spontaneous incidence xo xo+l xo xo+l ICRP 60 Part 1. Biological effects of ionizing radiation

Radiation Risks Radiation Protection in Nuclear Medicine Effect Population Exposure period Probability ICRP 1990 ICRP 2007 Hereditary effects Whole population Lifetime 1 %/Sv (all generations) 0.2 %/Sv Fatal cancer 5 %/Sv - Working population Age 18-65 4 %/Sv Health detriment 7.3 %/Sv 5.7 %/Sv 5.6 %/Sv 4.2 %/Sv The risk estimates derived by the ICRP Part 1. Biological effects of ionizing radiation

Risk (%/ Sv) for Cancer induction by Age at exposure and Sex
Part 1. Biological effects of ionizing radiation Risk (%/ Sv) for Cancer induction by Age at exposure and Sex Radiation Protection in Nuclear Medicine 20 15 10 5 Male Female 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. (age at exposure) Part 1. Biological effects of ionizing radiation

Life-time risk of dying from radiation induced cancer ≈ 5% per sievert
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Life-time risk of dying from radiation induced cancer ≈ 5% per sievert UNSCEAR has recently (2008) further assessed the cancer risk from radiation exposures. For a population of all ages and both genders, the lifetime 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. Part 1. Biological effects of ionizing radiation

Effects at Low Doses Radiation Protection in Nuclear Medicine In the latest Hiroshima-Nagasaki Life Span Study ( ), 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. Part 1. Biological effects of ionizing radiation

Uncertainties in Fatal Cancer Risk Estimate (5% per Sv)
Part 1. Biological effects of ionizing radiation Uncertainties in Fatal Cancer Risk Estimate (5% per Sv) Radiation Protection in Nuclear Medicine Frequency chart Trials Shown Probability 0.027 0.020 0.013 0.007 0.000 0.00 2.75 5.50 8.25 11.0 8.84 1.20 Lifetime Risk Coefficient (%/Sv) Probability distribution of lifetime risk coefficient. The 90% confidence interval is shown by the arrows (5% should be read as 1% - 9%). NCRP, 1997 Part 1. Biological effects of ionizing radiation

Uncertainties in Fatal Cancer Risk Estimates
Part 1. Biological effects of ionizing radiation Uncertainties in Fatal Cancer Risk Estimates Radiation Protection in Nuclear Medicine Sensitivity chart of uncertainty component influence (population of all ages) From NCRP, 1997 Part 1. Biological effects of ionizing radiation

Radiation Risks - Embryo and Fetus
Part 1. Biological effects of ionizing radiation Radiation Risks - Embryo and Fetus Radiation Protection in Nuclear Medicine Threshold dose deterministic effects mSv Mental retardation 40% / Sv Cancer and leukemia before 10 y of age 2% / Sv lifetime 15% / Sv Hereditary effects 1% / Sv Part 1. Biological effects of ionizing radiation

TYPES OF EFFECTS FOLLOWING IRRADIATION IN UTERO
Part 1. Biological effects of ionizing radiation TYPES OF EFFECTS FOLLOWING IRRADIATION IN UTERO Radiation Protection in Nuclear 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 weeks organsa (1 in 17) 8th through 25th Potential for severe mental x 10-3 weeks retardationb (1 in 200) 4th week throughout Cancer in childhood or in adult 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: th week c Risk in utero ~ risk < 10 years of age 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. Part 1. Biological effects of ionizing radiation

Radiation Risks Embryo and Fetus
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Radiation Risks Embryo and Fetus This figure can be used in a discussion of national policies regarding termination of pregnancy due to medical exposure. Other reasons 3* * * * Data from Sweden 1992 Part 1. Biological effects of ionizing radiation

Risks in a Pregnant Population not Exposed to Medical Radiation
Spontaneous abortion > 15% incidence of genetic abnormalities % intrauterine growth retardation % incidence of major malformation % Part 1. Biological effects of ionizing radiation

Probability of bearing healthy children as a function of radiation dose Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear 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 750 240 300 400 930 4.7 0.9 0.6 4.4 9.0 6.0 1.8 1.1 3.7 3.5 2.5 I-123 Thyroid uptake 30 0.3 I-131 Thyroid uptake 0.55 0.04 0.15 Part 1. Biological effects of ionizing radiation

Doses and Risks for in Utero Radiodiagnostics
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Doses and Risks for in Utero Radiodiagnostics Exposure Mean fetal dose Hered. Disease Fatal cancer (mGy) to age 14 y X-ray Abdomen Barium enema Barium meal IV urography Lumbar spine Pelvis Computed tomography Abdomen Lumbar spine Pelvis Nuclear medicine Tc bone scan Tc brain scan NRPB (1993) Board statement on diagnostic medical exposures during pregnancy, Documents of the NRPB, 4, 1-14. Part 1. Biological effects of ionizing radiation

Comment on Fetus/Embryo
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear 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 Part 1. Biological effects of ionizing radiation

Scale of Radiation Exposures
Part 1. Biological effects of ionizing radiation Scale of Radiation Exposures Radiation Protection in Nuclear Medicine Typical Radiotherapy Fraction Bone scan CT scan Annual Background Part 1. Biological effects of ionizing radiation

Example for Risk Calculation
Part 1. Biological effects of ionizing radiation Example for Risk Calculation Radiation Protection in Nuclear Medicine 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 Part 1. Biological effects of ionizing radiation

Radiation Risks in X-RAY Examination
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Radiation Risks in X-RAY Examination Examination Skin dose Effective dose Risk (mGy) (mGy) (%) Urography Lumbar spine Abdomen Chest Extremities Part 1. Biological effects of ionizing radiation

Radiation Risks in Nuclear Medicine
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear Medicine Radiation Risks in Nuclear Medicine Examination Radiopharmaceutical Effective dose Risk (mSv) (%) Myocardium Tl-201 chloride Bone Tc-99m MDP Thyroid Tc-99m pertechnetate Lungs Tc-99m MAA Kidney clearance Cr-51 EDTA Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear Medicine Average Annual Risk of Death in the UK from Industrial Accidents and from Cancers due to Radiation Work These figures can be compared to an estimate of 1 in for 1.5 mSv/year received by radiation workers From L Collins 2000 Part 1. Biological effects of ionizing radiation

Comparison of Radiation Worker Risks to Other Workers
Part 1. Biological effects of ionizing radiation Radiation Protection in Nuclear 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 exposure (20 mSv/year or 1000 mSv over a lifetime Part 1. Biological effects of ionizing radiation

Risks Radiation Protection in Nuclear Medicine The following activities are associated with a risk of death that is 1/ 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 Part 1. Biological effects of ionizing radiation

Risks Radiation Protection in Nuclear Medicine Expected reduction of life Unmarried man days Smoking man days Unmarried woman days 30% overweight days Cancer days Construction work days Car accident days Accident at home days Administrative work days Radiological examination days Part 1. Biological effects of ionizing radiation

Radiation Protection in Nuclear Medicine Questions?? Part 1. Biological effects of ionizing radiation

Discussion Radiation Protection in Nuclear Medicine 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. Part 1. Biological effects of ionizing radiation

Discussion Radiation Protection in Nuclear Medicine 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? Part 1. Biological effects of ionizing radiation

Discussion Radiation Protection in Nuclear Medicine A patient (radiobiologist) wants to know the radiation risk he will suffer in an examination of the cerebral blood flow (1000 MBq 99mTc). What to answer? Part 1. Biological effects of ionizing radiation

Where to Get More Information
Part 1. Biological effects of ionizing radiation Where to Get More Information Radiation Protection in Nuclear Medicine Other sessions Part 2 Radiation Physics Further readings WHO/IAEA. Manual on Radiation Protection in Hospital and General Practice. Volume 1. Basic requirements 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 (1989) 92-3. Part 1. Biological effects of ionizing radiation

RADIATION PROTECTION IN NUCLEAR MEDICINE

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