核医学辐射防护Radiation Protection in Nuclear Medicine

1、核医学辐射防护Radiation Protection in Nuclear MedicineNuclear MedicinePart 1. Biological effects of ionizing radiation2OBJECTIVETo become familiar with the mechanisms of different types of biological effects following exposure to ionizing radiation and results of epidemiological studies of exposed populati

2、on to ionizing radiation. To be aware of the models used to derive risk coefficients for estimating the detriment Nuclear MedicinePart 1. Biological effects of ionizing radiation3CONTENTBasic concepts, cellular effectsDeterministic effectsStochastic effectsEffects on embryo and fetusRisk estimatesIn

3、ternational Atomic Energy AgencyPart 1. Biological effects of ionizing radiation4Part 1. Biological effectsModule 1.1. Basic conceptsNuclear MedicinePart 1. Biological effects of ionizing radiation51895 X-rays discovered by Roentgen1896 First skin burns reported1896 First use of x-rays in the treatm

4、ent 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)Early Observat

5、ions of the Effects of Ionizing RadiationNuclear MedicinePart 1. Biological effects of ionizing radiation6Information comes from:studies of humans (epidemiology)studies of animals and plants (experimental radiobiology)fundamental studies of cells and their components(cellular and molecular biology)T

6、he key to understanding the health effects of radiation is the interaction between these sources of information.Effects of Radiation ExposureNuclear MedicinePart 1. Biological effects of ionizing radiation7ChromosomesNuclear MedicinePart 1. Biological effects of ionizing radiation8Nuclear MedicinePa

7、rt 1. Biological effects of ionizing radiation9The critical target: DNANuclear MedicinePart 1. Biological effects of ionizing radiation10Interaction of ionizing radiation with DNADIRECT ACTIONINDIRECT ACTIONNuclear MedicinePart 1. Biological effects of ionizing radiation11Damage to DNANuclear Medici

8、nePart 1. Biological effects of ionizing radiation12radiation hit cell nucleus!No changeDNA mutationExposure of the cellNuclear MedicinePart 1. Biological effects of ionizing radiation13DNA MutationCell survives but mutatedCancer?Cell deathMutation repairedUnviable CellViable Cell Outcomes after cel

9、l exposureNuclear MedicinePart 1. Biological effects of ionizing radiation14How is DNA repaired?Nuclear MedicinePart 1. Biological effects of ionizing radiation15 Altered baseEnzyme Glycosylases recognizes lesion and releases damaged baseAP-endunuclease makes incision and releases remaining sugarDNA

10、-polymerase fills resulting gap but nick remainsDNA ligase seals the nick. Repair completed. DNA has been repaired with no loss of genetic informationNuclear MedicinePart 1. Biological effects of ionizing radiation16RepairThe human body contains about 1014 cells. An absorbed dose of 1 mGy per year (

11、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. Nuclear MedicinePart 1. Biological effects of ionizi

12、ng radiation17 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)Nuclear MedicinePart 1. Biological effects of ionizing radiation18Cell killingRadi

13、osensitivityRS = 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.Nuclear MedicinePart 1. Biological effects of ionizing radiation19RADIOSENSITIVITYHigh RSMe

14、dium RSLow RSBone MarrowSpleenThymusLymphatic nodesGonadsEye lensLymphocytes (exception to the RS laws)SkinMesoderm organs (liver, heart, lungs)MuscleBonesNervous systemNuclear MedicinePart 1. Biological effects of ionizing radiation20Biological effects at cellular levelPossible mechanisms of cell d

15、eath: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%Nuclear MedicinePart 1. Biological effects of

16、ionizing radiation21PhysicalLET (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

17、% survivor cellsFactors affecting radiosensitivityNuclear MedicinePart 1. Biological effects of ionizing radiation22.Lg LETHg LETlow LEThigh LEThigh LETlow LETAbsorbed doseSurviving fractionLET (linear energy transfer) is the amount of energy (MeV) a particle will loose in traversinga certain distan

18、ce (m) of a material.CELL SURVIVALRadiation qualityNuclear MedicinePart 1. Biological effects of ionizing radiation23Adapted from Marco Zaider (2000)IONIZATION PATTERNNuclear MedicinePart 1. Biological effects of ionizing radiation24DirecteffectsIndirecteffectsCell deathPrimarydamageModifiedcellDama

19、geto organSomaticcellsGermcellsHereditaryeffectsCancerLeukemiaDeath oforganismRepairDeterministiceffectsStochasticeffectsBIOLOGICAL EFFECTSNuclear MedicinePart 1. Biological effects of ionizing radiation2510-610-1210-910-1510-31 second1 hour1 day1 year100 years1 ms100109106103Energy depositionExcita

20、tion/ionizationInitial particle tracksRadical formationPHYSICAL INTERACTIONSPHYSICO-CHEMICAL INTERACTIONSBIOLOGICAL RESPONSEMEDICAL EFFECTSDiffusion, chemical reactionsInitial DNA damageDNA breaks / base damageRepair processesDamage fixationCell killingPromotion/completionTeratogenesisCancerHeredita

21、ry defectsProliferation of damaged cellsMutations/transformations/aberrationsTIM E (sec)Timing of events leading to radiation effectsInternational Atomic Energy AgencyPart 1. Biological effects of ionizing radiation26Part 1. Biological effectsModule 1.2. Deterministic effectsNuclear MedicinePart 1.

22、Biological effects of ionizing radiation27Dose (mSv)Probability of deathD100%Nuclear MedicinePart 1. Biological effects of ionizing radiation28 012345678910 FREQUENCY ABSORBED DOSE SEVERITY Diagnostic threshold Threshold dose Most radiosensitive individual Most radioresistant individual Deterministi

23、c effectsNuclear MedicinePart 1. Biological effects of ionizing radiation29Cataracts 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 GydoseSeverity ofeffectthresholdThreshold Doses for Deterministic EffectsNuclear Medicine

24、Part 1. Biological effects of ionizing radiation30Note 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 personsN

25、uclear MedicinePart 1. Biological effects of ionizing radiation31Systemic effectsEffects may be morphological and/or functionalFactors:Which OrganWhich DoseEffects Immediate (usually reversible): 6 months e.g.: atrophy, sclerosis, fibrosis.Criteria of dose 10 Gy: HIGH DOSERegeneration means replacem

26、ent by the original tissue while Repair means replacement by connective tissue.Nuclear MedicinePart 1. Biological effects of ionizing radiation32Skin effectsF o l l o w i n g t h e R S l a w s (Bergonie and Tribondeau), the most RS cells are those from the basal stratum of the epidermis.Effects are:

27、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. DERMISEPIDERMIS

28、Histologic view of the skinBasal stratum cells, highly mitotic, some of them with melanin, responsible of pigmentation.From “Atlas de Histologia.”. J. BoyaNuclear MedicinePart 1. Biological effects of ionizing radiation33Skin effectsInjuryThreshold Dose to Skin (Sv)Weeks to OnsetEarly transient eryt

29、hema214Telangiectasis1252Moist desquamation154Late erythema156-10Dermal necrosis1810Secondary ulceration206Skin damagefrom prolongedfluoroscopicexposureNuclear MedicinePart 1. Biological effects of ionizing radiation34SKIN EFFECTSBy handling unshielded syringes and vials containing radioactive mater

30、ial the threshold dose of skin erythema will be reached in a short time.Example: The dose rate at the surface of a vialcontaining 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 yearNuclear Me

31、dicinePart 1. Biological effects of ionizing radiation35SKIN EFFECTSExampleAfter an extravascular injection of 500 MBq of a Tc99mradiopharmaceutical, the locally absorbed dose at theinjection site might be as high as 5-20 Gy!Nuclear MedicinePart 1. Biological effects of ionizing radiation36Effects i

32、n eyeEye lens is highly RS.Coagulation of proteins occur with doses greater than 2 Gy.There are 2 basic effects:From “Atlas de Histologia.”. J. BoyaHistologic view of eye:Eye lens is highly RS, moreover, it is surrounded by highly RS cuboid cells. 0.155.0Visual impairment (cataract) 0.10.5-2.0Detect

33、able opacitiesSv/year for many yearsSv single brief exposureEffectNuclear MedicinePart 1. Biological effects of ionizing radiation37Eye injuriesNuclear MedicinePart 1. Biological effects of ionizing radiation38Whole body response : adultAcute irradiation syndromeChronic irradiation syndromeSurvival

34、timeDoseSteps:ProdromicLatency1. ManifestationLethal dose 50 / 30BMS(bonemarrow)GIS(gastrointestinal)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 radiotherapyN

35、uclear MedicinePart 1. Biological effects of ionizing radiation39Lethal 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.Nucle

36、ar MedicinePart 1. Biological effects of ionizing radiation40Whole body exposureAbsorbed dose (Gy)Syndrome or tissue involvedSymptoms1-10Bone marrow syndromeLeucopenia, thrombopenia, hemorrhage, infections 10-50GastrointestinalDiarrhoea, fever, electrolytic imbalance50Central nervous syndromeCramps,

37、 tremor, ataxia, lethargy, impaired vision, comaNuclear MedicinePart 1. Biological effects of ionizing radiation41Whole body exposureAbsorbed dose (Gy)TherapyPrognosis1-10SymptomaticTransfusions of leucocytes and platelets. Bone marrow transplantationGrowth stimu-lating factorsExcellent touncertain1

38、0-50PalliativeVery poor50SymptomaticHopelessLethality0-90%90-100%100%International Atomic Energy AgencyPart 1. Biological effects of ionizing radiation42Part 1. Biological effectsModule 1.3. Stochastic effectsNuclear MedicinePart 1. Biological effects of ionizing radiation43STOCHASTIC EFFECTS OF ION

39、IZING RADIATIONNuclear MedicinePart 1. Biological effects of ionizing radiation44STOCHASTIC EFFECTS OF IONIZING RADIATIONHealth consequences of Chernobyl accident1800 children diagnosed with thyroid cancer (1998)Nuclear MedicinePart 1. Biological effects of ionizing radiation45STOCHASTIC EFFECTS OF

40、IONIZING RADIATIONThyroid cancer diagnosed up to 1998 among children 0-17 years at the time of the Chernobyl accident0501001502002503001990 1991 1992 1993 1994 1995 1996 1997 1998YearNumberBelarusRussian FederationUkraineTotal Nuclear MedicinePart 1. Biological effects of ionizing radiation46Frequen

41、cy (%) 10 20 30 40 Absorbed dose (Gy) 10 5 0Genetic effectsNuclear MedicinePart 1. Biological effects of ionizing radiation47Genetic EffectsIonising radiation is known to cause heritable mutations in many plants and animalsBUTintensive studies of 70,000 offspring of the atomic bomb survivors have fa

42、iled to identify an increase in congenital anomalies, cancer, chromosome aberrations in circulating lymphocytes or mutational blood protein changes.International Atomic Energy AgencyPart 1. Biological effects of ionizing radiation48Part 1. Biological effectsModule 1.4. Effects on embryo and fetusNuc

43、lear MedicinePart 1. Biological effects of ionizing radiation49Sensitivity 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 befor

44、e organogenesis high radiation exposure may lead to failure to implant. Low dose may not have any observable effect.Nuclear MedicinePart 1. Biological effects of ionizing radiation50Incidence of Prenatal & Neonatal Death and AbnormalitiesHall, Radiobiology for the Radiologist pg 365 Nuclear Medi

45、cinePart 1. Biological effects of ionizing radiation51PRE-IMPLANTATIONNuclear MedicinePart 1. Biological effects of ionizing radiation52Pre-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 resor

46、bedIf 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 Nuclear MedicinePart 1. Biological effects of ionizing radiation53Nuclear MedicinePart 1. Biological effects of ion

47、izing radiation54Fetal 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 t

48、rimesterLessLeastMost riskNuclear MedicinePart 1. Biological effects of ionizing radiation55Radiation-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 pelv

49、ic CT scans or 20 conventional diagnostic x-ray examinations These levels can be reached with fluoroscopically guided interventional procedures of the pelvis and with radiotherapyNuclear MedicinePart 1. Biological effects of ionizing radiation56Central Nervous System EffectsDuring 8-25 weeks post-co

50、nception 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 weeksNuclear M

51、edicinePart 1. Biological effects of ionizing radiation57Heterotopic gray matter (arrows) near the ventricles in a mentally retarded individual occurring as a result of high dose in-utero radiation exposure Nuclear MedicinePart 1. Biological effects of ionizing radiation58Effects on embryo and fetus

52、Nuclear MedicinePart 1. Biological effects of ionizing radiation59AgeThreshold for lethal effects (mGy)Threshold for malformations (mGy)1 day100No effect14 days250-18 days50025020 days50025050 days100050050 days to birth1000500Effects on embryo and fetusNuclear MedicinePart 1. Biological effects of

53、ionizing radiation60Leukemia 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 Nuclear MedicinePart 1. Biologi

54、cal effects of ionizing radiation61Leukemia 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 ute

55、ro” to 10 mGyInternational Atomic Energy AgencyPart 1. Biological effects of ionizing radiation62Part 1. Biological effectsModule 1.5. Risk estimatesNuclear MedicinePart 1. Biological effects of ionizing radiation63Risk EstimatesRisk = probability of effectDifferent effects can be looked at - one ne

56、eds 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 dosesNuclear MedicinePart 1. Biological effects of ionizing radiation64EPIDEMIOLOGICAL DATA FROM:Hiro

57、shima-NagasakiPatients withancylosing spondylitiscervical cancertuberculosismastitistinea capitisthymus enlargementthyrotoxicosishemangiomasand more may comeChernobylTecha riverSemiplatinskNevada.Nuclear MedicinePart 1. Biological effects of ionizing radiation65Populations used in the UNSCEAR Report

58、sCharacteristic Atomic Bomb Survivors Spondylitis Series Cervical Cancer Series Number 86,500 14,000 83,000 Age at irradiation 0 - 90 15 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

59、 Fractionated / partial-body Chronic / partial-body Nuclear MedicinePart 1. Biological effects of ionizing radiation66How to use epidemiological data to estimate radiation risks at low doses?Nuclear MedicinePart 1. Biological effects of ionizing radiation67Dose-response curveFrequency of leukemia (c

60、ases/1 miljon)Equivalent dose (mSv)Nuclear MedicinePart 1. Biological effects of ionizing radiation68Mortality 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