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RADIATION PROTECTION IN NUCLEAR MEDICINE

RADIATION PROTECTION IN NUCLEAR MEDICINE. Part 1: Biological Effects of Ionizing Radiation. Objective.

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RADIATION PROTECTION IN NUCLEAR MEDICINE

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  1. RADIATION PROTECTION IN NUCLEAR MEDICINE Part 1: Biological Effects of Ionizing Radiation

  2. Objective To become familiar with the mechanisms of different types of biological effects following exposure to ionizing radiation and results of epidemiological studies of exposed population to ionizing radiation. To be aware of the models used to derive risk coefficients for estimating the detriment Part 1. Biological effects of ionizing radiation

  3. Contents • Basic concepts, cellular effects • Deterministic effects • Stochastic effects • Effects on embryo and fetus • Risk estimates Part 1. Biological effects of ionizing radiation

  4. Part 1. Biological Effects Module 1.1. Basic Concepts

  5. Early Observations of the Effects of Ionizing Radiation • 1895 X-rays discovered by Roentgen • 1896 First skin burns reported • 1896 First use of x-rays in the treatment of cancer • 1896 Becquerel: Discovery of radioactivity • 1897 First cases of skin damage reported • 1902 First report of x-ray induced cancer • 1911 First report of leukaemia in humans and lung cancer from occupational exposure • 1911 94 cases of tumour reported in Germany (50 being radiologists) Part 1. Biological effects of ionizing radiation

  6. Effects of Radiation Exposure • 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

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

  8. Part 1. Biological effects of ionizing radiation

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

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

  11. Damage to DNA Part 1. Biological effects of ionizing radiation

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

  13. 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

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

  15. Altered base Enzyme Glycosylases recognizes lesion and releases damaged base AP-endunucleasemakes incision and releasesremaining sugar DNA-polymerasefillsresultinggap 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

  16. Repair The human body contains about 1014 cells. An absorbed dose of 1 mGy per year (natural sources) will produce about 1016 ionizations, which means 100 per cell in the body. If we assume that the mass of DNA is 1% of the mass of the cell, the result will be one ionization in the DNA-molecule in every cell in the body each year. Part 1. Biological effects of ionizing radiation

  17. … order of magnitudes • 999 of 1000 lesions are repaired • 999 of 1000 damaged cells die (not a major problem as millions of cells die every day in every person) • many cells may live with damage (could be mutated) Part 1. Biological effects of ionizing radiation

  18. Cell killingRadiosensitivity • 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

  19. RADIOSENSITIVITY Part 1. Biological effects of ionizing radiation

  20. Biological Effects at Cellular Level Possible mechanisms of cell death: • Physical death • Functional death • Death during interphase • Mitotic delay • Reproductive failure Cellular effects of ionizing radiation are studied bycell survival curves Exponential n = targets % survival cells (semi logarithmic) 100% Dq (threshold) D0 (radiosensitivity) Dose Part 1. Biological effects of ionizing radiation

  21. Factors Affecting Radiosensitivity • 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

  22. Cell SurvivalRadiation Quality 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

  23. Ionization Pattern Adapted from Marco Zaider (2000) Part 1. Biological effects of ionizing radiation

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

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

  26. Part 1. Biological Effects Module 1.2. Deterministic Effects

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

  28. Deterministic Effects 0 1 2 3 4 5 6 7 8 9 10 SEVERITY Most radiosensitive Most radioresistant individual individual Diagnostic threshold FREQUENCY Threshold ABSORBED DOSE dose Part 1. Biological effects of ionizing radiation

  29. Threshold Doses for Deterministic Effects Severity of effect dose threshold • Cataracts of the lens of the eye 0.5 Gy [ICRP statement on tissue reactions (http://www.icrp.org/docs/icrp%20statement%20on%20tissue%20reactions.pdf)] • Permanent sterility • males 3.5-6 Gy • females 2.5-6 Gy • Temporary sterility • males 0.15 Gy • females 0.6 Gy Part 1. Biological effects of ionizing radiation

  30. Note on Threshold Values • Depend on dose delivery mode: • single high dose most effective • fractionation increases threshold dose in most cases significantly • decreasing the dose rate increases threshold in most cases • Threshold may differ in different persons Part 1. Biological effects of ionizing radiation

  31. Systemic Effects • Effects may be morphological and/or functional • Factors: • Which Organ • Which Dose • Effects • Immediate (usually reversible): < 6 months e.g.: inflammation, bleeding. • Delayed (usually irreversible): > 6 months e.g.: atrophy, sclerosis, fibrosis. • Criteria of dose • < 1 Gy: LOW DOSE • 1-10 Gy: MODERATE DOSE • > 10 Gy: HIGH DOSE • Regeneration means replacement by the original tissue while Repair means replacement by connective tissue. Part 1. Biological effects of ionizing radiation

  32. Skin Effects EPIDERMIS DERMIS • 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 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

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

  34. Skin Effects By handling unshielded syringes and vials containing radioactive material the threshold dose of skin erythema will be reached in a short time. Example: The dose rate at the surface of a vial containing 30 GBq Tc99m is of the order of 2 Gy/h meaning that the threshold dose will be reached after 2 h of exposure. This corresponds to 36 s per working day in a year Part 1. Biological effects of ionizing radiation

  35. Skin Effects Example: After an extravascular injection of 500 MBq of a Tc99m radiopharmaceutical, the locally absorbed dose at the injection site might be as high as 5-20 Gy! Part 1. Biological effects of ionizing radiation

  36. Effects in Eye • 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 0.5-2.0 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. http://www.icrp.org/docs/icrp%20statement%20on%20tissue%20reactions.pdf Part 1. Biological effects of ionizing radiation

  37. Eye Injuries Part 1. Biological effects of ionizing radiation

  38. Whole Body Response : Adult 2 1 • Steps: • Prodromic • Latency • Manifestation Acute irradiation syndrome Chronic irradiation syndrome 1-10 Gy • 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(bonemarrow) GIS(gastrointestinal) Lethal dose 50 / 30 CNS (central nervous system) Dose Part 1. Biological effects of ionizing radiation

  39. Lethal Dose 50/30 • It is an expression of the per cent lethal dose as a function of time. • It means: “Dose which would cause death to 50% of the population in 30 days”. • Its value is about 2-3 Gy for humans for whole body irradiation. Part 1. Biological effects of ionizing radiation

  40. Whole Body Exposure Part 1. Biological effects of ionizing radiation

  41. Whole Body Exposure Part 1. Biological effects of ionizing radiation

  42. Part 1. Biological Effects Module 1.3. Stochastic Effects

  43. Stochatic Effects of Ionizing Radiation Part 1. Biological effects of ionizing radiation

  44. Stochatic Effects of Ionizing Radiation • Health consequences of Chernobyl accident • 1800 children diagnosed with thyroid cancer (1998) Part 1. Biological effects of ionizing radiation

  45. Stochatic Effects of Ionizing Radiation Part 1. Biological effects of ionizing radiation

  46. Genetic Effects Frequency (%) 10 5 0 10 20 30 40 Absorbed dose (Gy) Part 1. Biological effects of ionizing radiation

  47. 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. 1990, 46:1053-1072 Part 1. Biological effects of ionizing radiation

  48. Part 1. Biological Effects Module 1.4. Effects on Embryo and Fetus

  49. Sensitivity of the Early Conceptus • Till early 1980’s, early conceptus was considered to be very sensitive to radiation - although no one knew how sensitive? • Realization that: • organogenesis starts 3-5 weeks after conception • In the period before organogenesis high radiation exposure may lead to failure to implant. Low dose may not have any observable effect. Part 1. Biological effects of ionizing radiation

  50. Incidence of Prenatal & Neonatal Death and Abnormalities Hall, Radiobiology for the Radiologist pg 365 Part 1. Biological effects of ionizing radiation

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