01. biological effects (7,287 kb)

Radiation Protection in Nuclear Medicine

International Atomic Energy Agency

RADIATION PROTECTION IN NUCLEAR MEDICINEPart 1: Biological effects of ionizing radiation

Part 1. Biological effects of ionizing radiation

Nuclear Medicine

OBJECTIVETo 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


Nuclear Medicine

CONTENT

Basic concepts, cellular effectsDeterministic effectsStochastic effectsEffects on embryo and fetusRisk estimates



Part 1. Biological effectsModule 1.1. Basic concepts


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Early Observations of the Effects of Ionizing Radiation1895 X-rays discovered by Roentgen1896 First skin burns reported1896 First use of x-rays in the treatment of cancer1896 Becquerel: Discovery of radioactivity1897 First cases of skin damage reported1902 First report of x-ray induced cancer1911 First report of leukaemia in humans and lung cancer from occupational exposure1911 94 cases of tumour reported in Germany (50 being radiologists)


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Effects of Radiation ExposureInformation 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.


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Radiation exposure affects the center of life: the cell


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The critical target: DNA


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Interaction of ionizing radiation with DNADIRECT ACTIONINDIRECT ACTION


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Damage to DNA


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Exposure of the cellradiation hit cell nucleus!No changeDNA mutation


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Outcomes after cell exposureDNA MutationCell survives but mutatedCancer?Cell deathMutation repairedUnviable CellViable Cell


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How is DNA repaired?


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Altered baseEnzyme Glycosylases recognizes lesion and releases damaged baseAP-endunuclease makes incision and releases remaining sugarDNA-polymerase fills resulting gap but nick remainsDNA ligase seals the nick. Repair completed. DNA has been repaired with no loss of genetic information


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RepairThe 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.


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order of magnitudes999 of 1000 lesions are repaired999 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)


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Cell killingRadiosensitivityRS = 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.


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RADIOSENSITIVITY

High RSMedium RSLow RSBone MarrowSpleenThymusLymphatic nodesGonadsEye lensLymphocytes (exception to the RS laws)SkinMesoderm organs (liver, heart, lungs)MuscleBonesNervous system


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Biological effects at cellular levelPossible mechanisms of cell death:Physical deathFunctional death Death during interphaseMitotic delayReproductive failureCellular effects of ionizing radiation are studied by cell survival curves% survival cells (semi logarithmic) Dosen = targetsDqD0(threshold)(radiosensitivity)100%


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Factors affecting radiosensitivityPhysicalLET (linear energy transfer): RSDose rate: RSTemperature RSChemicalIncrease RS: OXYGEN, cytotoxic drugs.Decrease RS: SULFURE (cys, cysteamine)BiologicalCycle status: RS: G2, M RS: SRepair of damage (sub-lethal damage may be repaired e.g. fractionated dose)G1SG2MG0 LET LET% survivor cells


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CELL SURVIVALRadiation qualitylow LEThigh LEThigh LETlow LETAbsorbed doseSurviving fractionLET (linear energy transfer) is the amount of energy (MeV) a particle will loose in traversinga certain distance (m) of a material.


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IONIZATION PATTERNAdapted from Marco Zaider (2000)


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BIOLOGICAL EFFECTSDirecteffectsIndirecteffectsCell deathPrimarydamageModifiedcellDamageto organSomaticcellsGermcellsHereditaryeffectsCancerLeukemiaDeath oforganismRepairDeterministiceffectsStochasticeffects


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Timing of events leading to radiation effects



Part 1. Biological effectsModule 1.2. Deterministic effects


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EFFECTS OF CELL DEATHDose (mSv)Probability of deathD100%


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Deterministic effects FREQUENCY ABSORBED DOSE SEVERITY Diagnostic threshold Threshold dose Most radiosensitive individual Most radioresistant individual


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Threshold Doses for Deterministic EffectsCataracts of the lens of the eye 2-10 GyPermanent sterility males 3.5-6 Gy females 2.5-6 GyTemporary sterility males 0.15 Gyfemales 0.6 Gy


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Note on threshold valuesDepend on dose delivery mode:single high dose most effectivefractionation increases threshold dose in most cases significantlydecreasing the dose rate increases threshold in most casesThreshold may differ in different persons


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Systemic effectsEffects may be morphological and/or functionalFactors:Which OrganWhich DoseEffects 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 DOSE1-10 Gy: MODERATE DOSE> 10 Gy: HIGH DOSERegeneration means replacement by the original tissue while Repair means replacement by connective tissue.


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Skin effectsFollowing 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 GyAlopecia: 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 skinBasal stratum cells, highly mitotic, some of them with melanin, responsible of pigmentation.From Atlas de Histologia.... J. Boya


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Skin effectsSkin damagefrom prolongedfluoroscopicexposure


Sheet1

Radrisk.xls2/10/01

Reference [47, Table 4-3], [48, Figure 4], [w-y] Cancer Excess Mortality (Attributable to Radiation Dose) and Years of Life Lost by Age at Exposure (death per Sv)

Age at exposureMale Mortality, all cancers (death per Sv)Female Mortality, all cancers (death per Sv)Age range at exposureMean Age of Range at ExposureAverage years of life remaining (male) [42], [z]Average years of life remaining (female) [42], [z]Male Mortality, all cancers [x] (death per Sv)Female Mortality, all cancers [x] (death per Sv)Years of Life Lost (male) [aa]Years of Life Lost (female) [aa]

85855.316.660.0110.0090.000.00

InjuryThreshold Dose to Skin (Sv)Weeks to Onset

Early transient erythema252

Moist desquamation154

Late erythema156-10

Dermal necrosis18>10

Secondary ulceration20>6

[w] The mortality risk values for ages 0.15

5.0Visual impairment (cataract)> 0.10.5-2.0Detectable opacitiesSv/year for many yearsSv single brief exposureEffect


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Eye injuries


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Whole body response : adultAcute irradiation syndromeChronic irradiation syndromeSurvival timeDoseLethal dose 50 / 30BMS (bone marrow)GIS (gastro intestinal)CNS(central nervous system)1-10 Gy10-50 Gy> 50 GyWhole body clinic of a partial-body irradiationMechanism: Neurovegetative disorderSimilar to a sick feelingQuite frequent in fractionated radiotherapy


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Lethal dose 50 / 30It 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.


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Whole body exposure

Absorbed dose (Gy)Syndrome or tissue involvedSymptoms1-10Bone marrow syndromeLeucopenia, thrombopenia, hemorrhage, infections 10-50GastrointestinalDiarrhoea, fever, electrolytic imbalance>50Central nervous syndromeCramps, tremor, ataxia, lethargy, impaired vision, coma


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Whole body exposure

Absorbed dose (Gy)TherapyPrognosis1-10Symptomatic Transfusions of leucocytes and platelets. Bone marrow transplantationGrowth stimu-lating factorsExcellent to uncertain10-50PalliativeVery poor>50SymptomaticHopeless

Lethality

0-90%90-100%100%



Part 1. Biological effectsModule 1.3. Stochastic effects


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STOCHASTIC EFFECTS OF IONIZING RADIATION


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STOCHASTIC EFFECTS OF IONIZING RADIATIONHealth consequences of Chernobyl accident1800 children diagnosed with thyroid cancer (1998)


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STOCHASTIC EFFECTS OF IONIZING RADIATION


Diagr1

3552262

861027123

901055155

1301949198

1374759243

1474179267

1363682254

1464573264

1601998731998

Belarus

Russian Federation

Ukraine

Total

Year

Number

Thyroid cancer diagnosed up to 1998 among children 0-17 years at the time of the Chernobyl accident

Blad1

BelarusRussian FederationUkraineTotal

19903552262

1991861027123

1992901055155

19931301949198

19941374759243

19951474179267

19961363682254

19971464573264

199816073

Blad1

0000

0000

0000

0000

0000

0000

0000

0000

0000

Belarus

Russian Federation

Ukraine

Total

Year

Number

Thyroid cancer diagnosed up to 1998 among children 0-17 years at the time of the Chernobyl accident

Blad2

Blad3

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Genetic effectsFrequency (%) 10 20 30 40 Absorbed dose (Gy) 10

5

0


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Genetic EffectsIonising radiation is known to cause heritable mutations in many plants and animalsBUTintensive 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, 46:1053-1072



Part 1. Biological effectsModule 1.4. Effects on embryo and fetus


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Sensitivity of the early conceptusTill early 1980s, early conceptus was considered to be very sensitive to radiation - although no one knew how sensitive?Realization that:organogenesis starts 3-5 weeks after conceptionIn the period before organogenesis high radiation exposure may lead to failure to implant. Low dose may not have any observable effect.


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Incidence of Prenatal & Neonatal Death and AbnormalitiesHall, Radiobiology for the Radiologist pg 365


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PRE-IMPLANTATION


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Pre-implant stage (up to 10 days)Only lethal effect, all or noneEmbryo contains only few cells which are not specializedIf too many cell are damaged-embryo is resorbedIf only few killed-remaining pluripotent cells replace the cells loss within few cell divisionsAtomic Bomb survivors - high incidence of both - normal birth and spontaneous abortion


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Fetal Radiation RiskThere are radiation-related risks throughout pregnancy which are related to the stage of pregnancy and absorbed doseRadiation risks are most significant during organogenesis and in the early fetal period somewhat less in the 2nd trimester and least in the third trimesterLessLeastMost risk


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Radiation-Induced MalformationsMalformations 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


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Central Nervous System EffectsDuring 8-25 weeks post-conception the CNS is particularly sensitive to radiationFetal 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


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


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Effects on embryo and fetus


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Effects on embryo and fetus

AgeThreshold for lethal effects (mGy)Threshold for malformations (mGy)1 day100No effect14 days250-18 days50025020 days>50025050 days>100050050 days to birth>1000>500


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Leukemia and CancerRadiation has been shown to increase the risk for leukemia and many types of cancer in adults and childrenThroughout most of pregnancy, the embryo/fetus is assumed to be at about the same risk for carcinogenic effects as children


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Leukemia and CancerThe relative risk may be as high as 1.4 (40% increase over normal incidence) due to a fetal dose of 10 mGyIndividual 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 effectsModule 1.5. Risk estimates


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Risk EstimatesRisk = probability of effectDifferent 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


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EPIDEMIOLOGICAL DATA FROM:

Hiroshima-NagasakiPatients withancylosing spondylitiscervical cancertuberculosismastitistinea capitisthymus enlargementthyrotoxicosishemangiomas

and more may come

ChernobylTecha riverSemiplatinskNevada..


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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

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How to use epidemiological data to estimate radiation risks at low doses?


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Dose-response curveFrequency of leukemia (cases/1 miljon)Equivalent dose (mSv)


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Mortality of the Atomic Bomb SurvivorsDose response curve for Solid CancerThe dose response is linear up to about 3 Sv with a slope of 0.37 ERR/SvThe excess lifetime risk per Sv for those exposed at age 30 is estimated at 0.10 and 0.14 for males and females respectivelyThe lowest dose at which there is a statistically significant excess risk is shown to be 50 mSvPierce DA et al, Rad Res 1996; 146:1-27


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Latest news from the Hiroshima-Nagasaki cohort

Extra years 1986-1990There 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.

1945-19501950-90 (1986-90)Leukemia? 87 (3)Solid cancer?335 (88)------------------------------------------------------------------- 420

Risk for children/Risk for adults = 1.4 - 1.7


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RADIATION RISKSLinear-quadratic model


EMBED Excel.Chart.5 \s

Deterministic effects

Observations

_977852638.xls

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What happens at the low-dose end of the graph?Linear extrapolationThreshold doseLower risk per dose for low dosesHigher risk per dose for for low doses


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Low doses: 15%incidence of genetic abnormalities 4-10%intrauterine growth retardation 4%incidence of major malformation 2-4%


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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

Nuclear Medicine

Approximate fetal whole body dose (mGy) from common nuclear medicine procedures done in early and late pregnancy


Nuclear Medicine

Doses and Risks for in Utero RadiodiagnosticsExposure Mean foetal dose Hered. Disease Fatal cancer (mGy) to age 14 y X-ray Abdomen2.66.2 10-57.7 10-5Barium enema 163.9 10-44.8 10-4Barium meal2.86.7 10-58.4 10-5IV urography3.27.7 10-59.6 10-5Lumbar spine3.27.6 10-59.5 10-5Pelvis1.74.0 10-55.1 10-5Computed tomographyAbdomen8.01.9 10-42.4 10-4Lumbar spine2.45.7 10-57.1 10-5Pelvis256.1 10-47.7 10-4Nuclear medicine Tc bone scan3.37.9 10-41.0 10-4 Tc brain scan4.31.0 10-51.3 10-4


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Comment on Fetus/EmbryoFetus/embryo is more sensitive to ionizing radiation than the adult humanIncreased incidence of spontaneous abortion a few days after conceptionIncreased incidence Mental retardationMicrocephaly (small head size) especially 8-15 weeks after conceptionMalformations: skeletal, stunted growth, genitalHigher risk of cancer (esp. leukemia)Both in childhood and later life


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Scale of Radiation ExposuresAnnualBackgroundCT scanBone scanTypicalRadiotherapyFraction


Epidemiology

20000.1

20002

200020

2000200

20002000

20004000

200010000

natural cancer mortality

additional cancer deaths due to radiation

Dose (mGy)

Cancer deaths /year/1M people

alphabeta

0.97921896460.9605973005

0.95695395750.9223781486

0.93332668010.8853254159

0.90846401610.8494212872

0.88249690260.8146473164

0.85555919040.780984481

0.82778650670.7484132353

0.79931513440.7169135625

0.77028091960.6864650263

0.74081822070.6570468198

0.71105890820.6286378143

0.68113142720.601216606

0.65115992920.5747615614

0.62126348220.5492508611

0.59155536440.5246625421

0.56214244520.5009745388

0.53312465920.4781647216

0.50459457190.4562109348

0.47663704010.4350910324

0.44932896410.4147829117

0.42273913170.3952645466

0.39692814880.376514018

0.37194845360.358509543

0.34784440890.3412295026

0.32465246740.3246524674

0.30240140150.3087572221

0.28111259390.2935227881

0.26080037790.2789284449

0.24147242370.2649537491

0.22313016010.2515785531

0.20576922610.2387830213

0.18937994330.2265476457

0.17394780430.214853259

0.1594539680.2036810478

0.14587575690.1930125628

0.13318714960.1828297293

0.1213592650.1731148555

0.1103608310.1638506396

0.1001586350.1550201764

0.09071795330.1466069621

0.08200295470.1385948985

0.07397707730.130968296

0.06660337680.1237118757

0.0598448440.1168107705

0.05366469190.1102505253

0.04802661220.1040170969

0.04289500040.0980968523

0.03823515110.0924765667

0.03401342430.087143421

0.03019738340.0820849986

0.02675590720.077289281

0.02365927650.0727446438

0.02087923820.0684398515

0.01838904820.064364052

0.01616349460.0605067712

0.01417890470.056857906

0.01241313620.0534077186

0.01084555460.0501468288

0.00945700070.0470662074

0.0082297470.0441571684

0.00714744740.0414113616

0.00619507910.0388207648

0.00535888150.0363776756

0.00462629010.0340747036

0.00398586870.031904762

0.003427240.0298610597

0.00294101650.0279370923

0.00251873120.0261266347

0.00215276980.0244237319

0.00183630480.0228226914

0.00156323170.0213180745

0.00132810790.0199046879

0.00112609430.0185775763

0.00095290060.0173320134

0.0008047330.0161634946

0.00067824630.0150677286

0.00057049850.0140406301

0.0004789090.0130783119

0.00040122030.0121770774

0.00033546260.0113334132

0.00027992190.0105439821

0.000233110.009805616

0.00019373870.0091153087

0.00016069540.0084702098

0.00013302150.0078676175

0.00010989340.0073049725

0.00009060510.006779852

0.0000745530.0062899636

0.00006122220.005833139

0.00005017470.0054073291

0.00004103850.005010598

0.00003349880.004641118

0.00002728970.004297164

0.00002218710.0039771094

0.00001800250.0036794205

0.0000145780.0034026525

0.00001178130.0031454447

0.00000950210.0029065165

0.00000764850.0026846632

0.00000614420.0024787522

cell kill (low a/b)

cell kill (high a/b)

Dose (Gy)

Probability of cell survival

fractionated

0.97921896460.960597300511

0.95695395750.92237814860.97921896460.9605973005

0.93332668010.88532541590.95695395750.9223781486

0.90846401610.84942128720.93332668010.8853254159

0.88249690260.81464731640.90846401610.8494212872

0.85555919040.7809844810.88249690260.8146473164

0.82778650670.74841323530.85555919040.780984481

0.79931513440.71691356250.82778650670.7484132353

0.77028091960.68646502630.79931513440.7169135625

0.74081822070.65704681980.77028091960.6864650263

0.71105890820.62863781430.74081822070.6570468198

0.68113142720.6012166060.71105890820.6286378143

0.65115992920.57476156140.68113142720.601216606

0.62126348220.54925086110.65115992920.5747615614

0.59155536440.52466254210.62126348220.5492508611

0.56214244520.50097453880.59155536440.5246625421

0.53312465920.47816472160.56214244520.5009745388

0.50459457190.45621093480.53312465920.4781647216

0.47663704010.43509103240.50459457190.4562109348

0.44932896410.41478291170.47663704010.4350910324

0.42273913170.39526454660.44932896410.4147829117

0.39692814880.3765140180.4399914430.3984393452

0.37194845360.3585095430.42998713040.3825866942

0.34784440890.34122950260.41937071030.3672178538

0.32465246740.32465246740.40819919530.3523254347

0.30240140150.30875722210.39653141910.3379017859

0.28111259390.29352278810.38442752480.323939017

0.26080037790.27892844490.37194845360.3104290209

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0.22313016010.25157855310.34610952770.2847339624

0.20576922610.23878302130.33287108370.272531793

0.18937994330.22654764570.31949936270.260748223

0.17394780430.2148532590.30605207860.2493743744

0.1594539680.20368104780.29258501650.238401274

0.14587575690.19301256280.27915167690.2278198714

0.13318714960.18282972930.26580295910.2176210569

0.1213592650.17311485550.25258688260.2077956779

0.1103608310.16385063960.23954835090.1983345555

0.1001586350.15502017640.22672895630.1892284999

0.09071795330.14660696210.21416682750.1804683252

0.08200295470.13859489850.2018965180.1720448638

0.07397707730.1309682960.19770089930.1652658317

0.06660337680.12371187570.19320567190.158690423

0.0598448440.11681077050.18843540690.1523156906

0.05366469190.11025052530.18341572160.1461385697

0.04802661220.10401709690.17817305180.1401558866

0.04289500040.09809685230.17273442150.1343643687

0.03823515110.09247656670.16712721330.1287606531

0.03401342430.0871434210.16137894240.1233412962

0.03019738340.08208499860.15551703550.118102782

0.02675590720.0772892810.14956861920.1130415306

0.02365927650.07274464380.14356031770.1081539072

0.02087923820.06843985150.13751806340.1034362291

0.01838904820.0643640520.13146692240.0988847746

0.01616349460.06050677120.12543093380.0944957896

0.01417890470.0568579060.11943296830.0902654956

0.01241313620.05340771860.11349460230.0861900963

0.01084555460.05014682880.10763601230.0822657844

0.00945700070.04706620740.10187588710.0784887482

0.0082297470.04415716840.09623135870.0748551774

0.00714744740.04141136160.09071795330.0713612696

0.00619507910.03882076480.08883274030.0685494429

0.00535888150.03637767560.08681290440.0658220757

0.00462629010.03407470360.08466948620.0631779456

0.00398586870.0319047620.08241399620.0606157814

0.003427240.02986105970.08005831280.0581342667

0.00294101650.02793709230.07761457870.0557320441

0.00251873120.02612663470.07509509760.0534077186

0.00215276980.02442373190.0725122330.051159862

0.00183630480.02282269140.06987830850.0489870158

0.00156323170.02131807450.06720551270.0468876952

0.00132810790.01990468790.06450580880.0448603925

0.00112609430.01857757630.0617908490.0429035803

0.00095290060.01733201340.0590718960.0410157147

0.0008047330.01616349460.05635975160.0391952388

0.00067824630.01506772860.05366469190.0374405851

0.00057049850.01404063010.05099641210.0357501791

0.0004789090.01307831190.04836397790.0341224416

0.00040122030.01217707740.04577578680.0325557915

0.00033546260.01133341320.04323953670.0310486484

0.00027992190.01054398210.0407622040.0295994352

0.000233110.0098056160.03991512320.0284331375

0.00019373870.00911530870.03900755240.0273018722

0.00016069540.00847020980.03804445250.0262051322

0.00013302150.00786761750.03703099550.0251423903

0.00010989340.00730497250.03597251880.0241131004

0.00009060510.0067798520.03487447820.0231166995

0.0000745530.00628996360.03374240240.022152609

0.00006122220.0058331390.03258184660.0212202365

0.00005017470.00540732910.0313983480.020318977

0.00004103850.0050105980.03019738340.0194482147

0.00003349880.0046411180.02898432830.0186073242

0.00002728970.0042971640.02776441820.017795672

0.00002218710.00397710940.02654271390.0170126176

0.00001800250.00367942050.02532406880.0162575153

0.0000145780.00340265250.02411310040.0155297149

0.00001178130.00314544470.0229141650.0148285634

0.00000950210.00290651650.02173133610.0141534057

0.00000764850.00268466320.02056838690.013503586

0.00000614420.00247875220.01942877630.0128784488

0.01831563890.0122773399

cell kill (low a/b)

cell kill (high a/b)

fractionated (low a/b)

fractionated (low a/b)

Dose (Gy)

Probability of cell survival

Sheet1

natural cancer mortalityadditional cancer deaths due to radiation

0.12000

120002

10200020

1002000200

100020002000

200020004000

100002000

alpha0.20.40.20.4

beta0.10.020.10.02

a/b220220

N1111

dose

cell kill (low a/b)cell kill (high a/b)fractionated (low a/b)fractionated (low a/b)

01111

0.10.97921896460.96059730050.97921896460.9605973005

0.20.95695395750.92237814860.95695395750.9223781486

0.30.93332668010.88532541590.93332668010.8853254159

0.40.90846401610.84942128720.90846401610.8494212872

0.50.88249690260.81464731640.88249690260.8146473164

0.60.85555919040.7809844810.85555919040.780984481

0.70.82778650670.74841323530.82778650670.7484132353

0.80.79931513440.71691356250.79931513440.7169135625

0.90.77028091960.68646502630.77028091960.6864650263

10.74081822070.65704681980.74081822070.6570468198

1.10.71105890820.62863781430.71105890820.6286378143

1.20.68113142720.6012166060.68113142720.601216606

1.30.65115992920.57476156140.65115992920.5747615614

1.40.62126348220.54925086110.62126348220.5492508611

1.50.59155536440.52466254210.59155536440.5246625421

1.60.56214244520.50097453880.56214244520.5009745388

1.70.53312465920.47816472160.53312465920.4781647216

1.80.50459457190.45621093480.50459457190.4562109348

1.90.47663704010.43509103240.47663704010.4350910324

20.44932896410.41478291170.44932896410.4147829117

2.10.42273913170.39526454660.4399914430.3984393452

2.20.39692814880.3765140180.42998713040.3825866942

2.30.37194845360.3585095430.41937071030.3672178538

2.40.34784440890.34122950260.40819919530.3523254347

2.50.32465246740.32465246740.39653141910.3379017859

2.60.30240140150.30875722210.38442752480.323939017

2.70.28111259390.29352278810.37194845360.3104290209

2.80.26080037790.27892844490.35915544130.2973634949

2.90.24147242370.26495374910.34610952770.2847339624

30.22313016010.25157855310.33287108370.272531793

3.10.20576922610.23878302130.31949936270.260748223

3.20.18937994330.22654764570.30605207860.2493743744

3.30.17394780430.2148532590.29258501650.238401274

3.40.1594539680.20368104780.27915167690.2278198714

3.50.14587575690.19301256280.26580295910.2176210569

3.60.13318714960.18282972930.25258688260.2077956779

3.70.1213592650.17311485550.23954835090.1983345555

3.80.1103608310.16385063960.22672895630.1892284999

3.90.1001586350.15502017640.21416682750.1804683252

40.09071795330.14660696210.2018965180.1720448638

4.10.08200295470.13859489850.19770089930.1652658317

4.20.07397707730.1309682960.19320567190.158690423

4.30.06660337680.12371187570.18843540690.1523156906

4.40.0598448440.11681077050.18341572160.1461385697

4.50.05366469190.11025052530.17817305180.1401558866

4.60.04802661220.10401709690.17273442150.1343643687

4.70.04289500040.09809685230.16712721330.1287606531

4.80.03823515110.09247656670.16137894240.1233412962

4.90.03401342430.0871434210.15551703550.118102782

50.03019738340.08208499860.14956861920.1130415306

5.10.02675590720.0772892810.14356031770.1081539072

5.20.02365927650.07274464380.13751806340.1034362291

5.30.02087923820.06843985150.13146692240.0988847746

5.40.01838904820.0643640520.12543093380.0944957896

5.50.01616349460.06050677120.11943296830.0902654956

5.60.01417890470.0568579060.11349460230.0861900963

5.70.01241313620.05340771860.10763601230.0822657844

5.80.01084555460.05014682880.10187588710.0784887482

5.90.00945700070.04706620740.09623135870.0748551774

60.0082297470.04415716840.09071795330.0713612696

6.10.00714744740.04141136160.08883274030.0685494429

6.20.00619507910.03882076480.08681290440.0658220757

6.30.00535888150.03637767560.08466948620.0631779456

6.40.00462629010.03407470360.08241399620.0606157814

6.50.00398586870.0319047620.08005831280.0581342667

6.60.003427240.02986105970.07761457870.0557320441

6.70.00294101650.02793709230.07509509760.0534077186

6.80.00251873120.02612663470.0725122330.051159862

6.90.00215276980.02442373190.06987830850.0489870158

70.00183630480.02282269140.06720551270.0468876952

7.10.00156323170.02131807450.06450580880.0448603925

7.20.00132810790.01990468790.0617908490.0429035803

7.30.00112609430.01857757630.0590718960.0410157147

7.40.00095290060.01733201340.05635975160.0391952388

7.50.0008047330.01616349460.05366469190.0374405851

7.60.00067824630.01506772860.05099641210.0357501791

7.70.00057049850.01404063010.04836397790.0341224416

7.80.0004789090.01307831190.04577578680.0325557915

7.90.00040122030.01217707740.04323953670.0310486484

80.00033546260.01133341320.0407622040.0295994352

8.10.00027992190.01054398210.03991512320.0284331375

8.20.000233110.0098056160.03900755240.0273018722

8.30.00019373870.00911530870.03804445250.0262051322

8.40.00016069540.00847020980.03703099550.0251423903

8.50.00013302150.00786761750.03597251880.0241131004

8.60.00010989340.00730497250.03487447820.0231166995

8.70.00009060510.0067798520.03374240240.022152609

8.80.0000745530.00628996360.03258184660.0212202365

8.90.00006122220.0058331390.0313983480.020318977

90.00005017470.00540732910.03019738340.0194482147

9.10.00004103850.0050105980.02898432830.0186073242

9.20.00003349880.0046411180.02776441820.017795672

9.30.00002728970.0042971640.02654271390.0170126176

9.40.00002218710.00397710940.02532406880.0162575153

9.50.00001800250.00367942050.02411310040.0155297149

9.60.0000145780.00340265250.0229141650.0148285634

9.70.00001178130.00314544470.02173133610.0141534057

9.80.00000950210.00290651650.02056838690.013503586

9.90.00000764850.00268466320.01942877630.0128784488

100.00000614420.00247875220.01831563890.0122773399

Sheet2

BED calculation

n1515

d8283.1

a/b202022

BED11.2114039.525

Sheet3

Nuclear Medicine

Example for Risk CalculationAssumeRisk of 0.05 per Sv1,000 people are exposed to 5 mSv/y for 20 yExpected additional cancer deaths is0.05 [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


Nuclear Medicine

RADIATION RISKS IN X-RAY EXAMINATIONSExamination Skin dose Effective dose Risk (mGy) (mGy) (%)

Urography 30 8 0.04Lumbar spine 40 5 0.025Abdomen 10 2.5 0.013Chest 2 0.25 0.0013Extremities 3 0.025 0.00013


Nuclear Medicine

RADIATION RISKS IN NUCLEAR MEDICINEExamination Radiopharmaceutical Effective dose Risk (mSv) (%)

Myocardium Tl-201 chloride 23 0.12Bone Tc-99m MDP 3.6 0.018Thyroid Tc-99m pertechnetate 1.1 0.006Lungs Tc-99m MAA 0.9 0.005Kidney clearance Cr-51 EDTA 0.01 0.00005


Nuclear Medicine

Average Annual Risk of Death in the UK from Industrial Accidents and from Cancers due to Radiation WorkFrom L Collins 2000

These figures can be compared to an estimate of 1 in 17000 for 1.5 mSv/year received by radiation workers


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

Nuclear Medicine

Comparison of Radiation Worker Risks to Other WorkersMean death rate 1989(10-6/y)Trade40Manufacture60Service40Government90Transport/utilities240Construction320Agriculture 400Mines/quarries430Safe industries 2 mSv/y (100 mSv over a lifetime) max permissible exposure (20 mSv/year or 1000 mSv over a lifetime


Nuclear Medicine

RISKSThe following activities are associated witha risk of death that is 1/100000010 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


Nuclear Medicine

RISKSExpected reduction of lifeUnmarried man3500 daysSmoking man2250 daysUnmarried woman1600 days30% overweight1300 daysCancer 980 daysConstruction work 300 daysCar accident 207 daysAccident at home 95 daysAdministrative work 30 daysRadiological examination 6 days


Nuclear Medicine

Questions??


Nuclear Medicine

DISCUSSIONA 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.


Nuclear Medicine

DISCUSSIONDose 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?


Nuclear Medicine

DISCUSSIONA 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?


Nuclear Medicine

Where to Get More InformationOther sessionsPart 2 Radiation PhysicsFurther readingsWHO/IAEA. Manual on Radiation Protection in Hospital and General Practice. Volume 1. Basic requirements (draft manuscript)ICRP publications (41, 60, 84)UNSCEAR reportsALPEN E.L Radiation Biophysics. Academic Press, 1998 RUSSEL, J.G.B., Diagnostic radiation, pregnancy and termination, Br. J. Radiol. 62 733 (1989) 92-3.


Part 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiation


Part 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationThe 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 radiationAnother 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 radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationThe 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 betweenPart 1. Biological effects of ionizing radiationThe 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.Part 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationThe 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.Part 1. Biological effects of ionizing radiationThis 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 radiationThe second point can be compared to drug effectsPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationThe 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 radiationSome data concerning the stochastic effects among people affected by the Chernobyl accident.Part 1. Biological effects of ionizing radiationThe 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 radiationThe 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.Part 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationThe lecturer can point out that this is animal data published in 1954Part 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationThe 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 radiationEstimated threshold doses. Data are primarily based on animal experimentsPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationA listing of the different groups of exposed humans used to estimate the risk of stochastic effects.Part 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationThe 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.Part 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationThe figure illustrates the concept of DDREF and the linear non threshold dose response curve.Part 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationThe 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 radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationPart 1. Biological effects of ionizing radiationThis 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.Part 1. Biological effects of ionizing radiationThe risk estimates derived by the ICRPPart 1. Biological effects of ionizing radiationThe 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