Ionizing Radiation. Nuclear Medicine

Transcription

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2 Ionizing Radiation Nuclear Medicine

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4 Somatic Deterministic Effect Erythema

5 Somatic Stochastic Effect Leukemia

6 Genetic Effects DNA

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8 BIOLOGICAL EFFECTS OF IONIZING RADIATION ON TISSUES, ORGANS AND SYSTEMS

9 Bergonié and Tribondeaus law (1906) The most radiosensitive cells are actively proliferating/dividing at the time of exposure undifferentiated (non-specialized in structure and function)

10 Types of cellular damage repair Altered Metabolism& function Cell death Reproductive cell death Mutation

11 Radiosensitivity of tissues Bone marrow Skin CNS Highly radiosensitive Lymphoid tissue Bone marrow Gastrointestinal epithelium Gonads Embryonic tissues Moderately radiosensitive Skin Vascular endothelium Lung Kidney Liver Lens (eye) Least radiosensitive Central nervous system (CNS) Muscle Bone and cartilage Connective tissue

12 Irradiated bone marrow Normal bone marrow Irradiated bone marrow lacks all precursor haematopoietic cells

13 Effects of radiation on lymphatic tissue A B Normal monkey lymph node C D Germinal centre of normal monkey lymph node Lymphoid cells depleted in cortex of canine lymph node Germinal centre of irradiated human lymph node

14 Early changes in peripheral blood lymphocyte counts Gy Gy 2-4 Gy 4-6 Gy >6 Gy

15 Lymphocyte changes as a function of dose <1 Gy 1-2 Gy 2-5 Gy >5-6 Gy Time after exposure (days)

16 Relative Number of Cells Model of blood renewal system Cell pools in normal steady state Dividing Stem Maturing & Blood cell maturing only? 2 days 1 day 1 day 1 day Transit timea Changes after irradiation Time After Irradiation 1 hour 1 day 2 days 3 days 4 1 / 4 days 5 days

17 Erythropoietic effects 3 Gy 1 Gy Erythropoietic response to 1Gy and 3Gy whole body exposure

18 Leukopoietic effects >5-6 Gy 2-5 Gy Normal <1Gy 1-2 Gy Time after exposure (days) Smoothed average of neutrophil changes in human cases of accidental radiation exposure as a function of dose

19 Thrombopoietic effects <1Gy Normal 2-5 Gy 1-2 Gy >5-6 Gy Time after exposure (Days) Smoothed average of platelet changes in human cases of accidental radiation exposure as a function of dose

20 The foetus Typical effects of radiation on embryo: Intrauterine growth retardation (IUGR) Embryonic, foetal, or neonatal death Congenital malformations

21 Effects of radiation according to gestational stage Gestational age Stage Radiogenic effects 0-9 days Preimplantation All or none 10 days- 6 weeks 6 weeks- 40 weeks Organogenesis foetal Congenital anomalies, growth retardation Growth retardation, microcephly, mental retardation

22 Considerations for pregnancy termination Threshold dose for developmental effects approximately 0.1 Gy Normal rate of preclinical loss >30%. At 0.1 Gy, increase of 0.1-1% The foetal absorbed dose > 0,5 Gy at 7-13 weeks: substantial risk of IUGR and CNS damage Gy at 7-13 weeks: physician s guidance parental decision with

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24 Radiation quality

25 Relation between LET and action type Direct action is predominant with high LET radiation, e.g. alpha particles and neutrons Indirect action is predominant with low LET radiation, e.g. X and gamma rays

26 Biochemical reactions with ionizing radiation DNA is primary target for cell damage from ionizing radiation

27 Types of radiation induced lesions in DNA Base damage Single-strand breaks Double strand breaks

28 DNA restoration failure Unrejoined DNA double strand breaks Incorrect repair of DNA damage Cytotoxic effect Mutations

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30 Dose rate and fractionation Acute exposure with high dose rate Time Prolonged exposure with lower dose rate 0 Acute dose Fractionated dose Time

31 Effects of radiation on cells at atomic level Excitation Ionization

32 Mechananisms of damage at molecular level

33 Direct action Ionizing radiation + RH R - + H + OH I R C = NH imidol (enol) Bond breaks Tautomeric Shifts O II R C = NH 2 amide (ketol)

34 Indirect action e - X ray O ray P + H H OH - H + H o OH o

35 Radiolysis of H 2 O Shared electron molecule H-O-H H + + OH - H-O-H H 0 +OH 0 Shared electron (ionization) (free radicals)

36 Reactions with free radicals H 0 + OH 0 HOH (recombination) H 0 + H 0 H 2 (dimer) OH 0 + OH 0 H 2 O 2 (hydrogen peroxide) OH 0 +RH R 0 +HOH (radical transfer)

37 Effects of oxygen on free radical formation Oxygen can modify the reaction by enabling creation of other free radical species with greater stability and longer lifetimes H 0 +O 2 HO 20 (hydroperoxy free radical) R 0 +O 2 RO 20 (organic peroxy free radical)

38 Because short life of simple free radicals (10-10 sec), only those formed in water column of 2-3 nm around DNA are able to participate in indirect effect Lifetimes of free radicals HO 2 o RO 2 o H o OH o 3nm OH o H o

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40 DOSE-EFFECT CURVES; DETERMINISTIC AND STOCHASTIC EFFECTS OF RADIATION

41 Biological effects of radiation in time perspective Time scale Effects Fractions of seconds Seconds Energy absorption Changes in biomolecules (DNA, membranes) Biological repair Minutes Change of information in cell Hours Days Weeks Months Years Decades Generations Cell death Organ Clinical death changes Mutations in a Germ cell Somatic cell Hereditary effects Leukaemia or Cancer

42 Radiation effects Early (deterministic only) Late Local Radiation injury of individual organs: functional and/or morphological changes within hrs-days-weeks Common Acute radiation disease Acute radiation syndrome (LD 50/60 ~ 3.5Sv LD ~ 5 Sv) Deterministic (Above D Q, cummul. ) - Rad. Dermatitis - Rad. Cataracta - Teratogenic (D Q,F ~0,1Sv) Stochastic (Probability increases with dose) - tumours, leukaemia - genetic effects

43 Threshold doses for some deterministic effects in the most radiosensitive tissues Tissue and Total dose Annual dose rate received effects single brief in highly fractionated or exposure (Gy) protracted exposure for many years (Gy/y) Bone marrow: Depression of 0.5 > 0.4 haematopoesis Testes: Temporary sterility Permanent sterility

44 Threshold doses for some deterministic effects Ovaries: Tissue and Total dose Annual dose rate received in received yearly in effects single brief highly fractionated or exposure (Gy) protracted exposure for many years (Gy/y) Sterility > 0.2 Lens: Detectable opacities 2.0 > 0.1 Visual impairment 5.0 > 0.4 (cataract)

45 Time of onset of clinical signs of skin injury depending on dose received Symptoms Dose range Time of onset (Gy) (day) Erythema Epilation > Dry desquamation Moist desquamation Blister formation Ulceration > Necrosis >25 >21 Ref.: IAEA-WHO: Diagnosis and Treatment of Radiation Injuries. IAEA Safety Reports Series, No. 2, Vienna, 1998

46 Acute radiation syndrome (ARS) ARS is the most notable deterministic effect of ionizing radiation Signs and symptoms are not specific for radiation injury but collectively highly characteristic of ARS Combination of symptoms appears in phases during hours to weeks after exposure - prodromal phase - latent phase - manifest illness - recovery (or death) Extent and severity of symptoms determined by - total radiation dose received - how rapidly dose delivered (dose rate) - how dose distributed in body (whole vs partial body irradiation)

47 Principle syndromes contributing to death after acute whole body radiation exposure Whole body dose, Gy Syndrome Time of death after the exposure - days 3-10 bone marrow gastrointestinal tract >30 neurovascular system 1-5

48 Special deterministic effects Teratogenic effects of radiation

49 Stochastic effects Cancer induction and genetic effects

50 Phases of cancer induction and manifestation Normal Cells Initiation Pre-cancer Mutated Cells Elimiation Reparation Promotion Minimal Cancer Clinical Cancer Progre ssion Spreading

51 Stochastic Effects of Radiation Exposure Frequency proportional to dose No threshold dose No method for identification of appearance of effect of ionizing radiation in individuals Increase in occurrence of stochastic effects provable only by epidemiological method

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53 Stochastic effects of radiation exposure (continued) Stochastic effects observed in animal experiments Dose-effect relationship for humans can be studied only in human population groups Dose-effect relationship in low dose range (below 100 msv) not yet verified Extrapolation down to zero excess dose accepted only for radiation protection and safety

54 Risk of leukaemia depending on age at exposure to A-bomb

55 Lifetime mortality in population of all ages from cancer after exposure to low doses Organ or tissue Bladder Bone Marrow Bone Surface Breast Colon Liver Oesophagus Ovary Skin Stomach Thyroid Remainder 1 Total Fatal Cancer Probability Coefficient (10-4 Sv -1 ) * * For general public (all age groups) only Summary factor of cancer risk for working population taken to be 400x10-4 Sv -1 Reference ICRP, Publ. 60, 1991

56 Genetic radiation damage Increase of chromosome aberrations in human spermatogonia following radiation exposure of testes has been detected inheritance of radiation damage in human population (including A-bomb survivors) not yet detected

57 Review of topics discussed Biological effects of radiation in time perspective Main characteristics of deterministic and stochastic effects Sources of data on human effects of radiation overexposure Threshold doses of deterministic effects in the most radiosensitive tissues Teratogenic effects of radiation: severe mental retardation, microcephaly Phases of cancer induction Sources of human data on radiation cancerogenesis (3 groups) Latency periods of radiation induced cancers (lag 2 & 10 yrs) Risk of cancer depending on age at exposure (reverse dependence) Cancer deaths attributable to A-bombs 5.4% in 40-yr follow up Cancer mortality studies of nuclear industry workers and offspring leukaemia probable in workers Genetic effects of radiation not proved in human population

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