Radiopharmaceuticals. Radionuclides in NM. Radionuclides NUCLEAR MEDICINE. Modes of radioactive decays DIAGNOSTIC THERAPY CHEMICAL COMPOUND

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1 Univerzita Karlova v Praze - 1. Lékařská fakulta Radiation protection NUCLEAR MEDICINE Involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear medicine study involves application of radiopharmaceuticals into the body. Aplication of Radiopharmaceuticals: most often: intravenously also: by inhalation ( 81m Kr) or orally ( 131 I) Nuclear medicine Ing. Daniela Skibová, Ph.D. 2015/2016 RADIONUCLIDE emit: Radiopharmaceuticals 99m Tc MDP (methylendiphosphonate) 99m Tc DMSA (dimerkaptosukcinát) 111 In - pentetreotid (OCTREOSCAN) γ-ray (gama) = diagnostic β - (α)-ray = therapy CHEMICAL COMPOUND = localize specific organs or cellular receptors Radionuclides in NM DIAGNOSTIC THERAPY SPECT PET 99m 131 Tc 18 F I 111 In, 123 I, 81m Kr 11 C, 13 N 15 O 90 Y, 186 Re, 177 Lu The photon energies useful for diagnostic procedures are generally in the range of 100 kev to 500 kev. Radionuclides Modes of radioactive decays RADIOACTIVE Radioactive decay: spontaneous process the process by which a nucleus of an unstable atom loses energy by emitting particles and/or photons. 4 He (2 p n 0 ) α Nucleus β (e - ), β + (e + ) β photons γ 1

2 Modes of radioactive decays ACTIVITY (A) α 4 He ( 223 Ra) β β e - ( 131 I) β + e + ( 18 F) PET THERAPY represents the amount of radionuclide which was apllied = the number of radioactive atoms (N) decaying per unit time (t): A = N/t (SI) Unit: Bq = Becquerel [s -1 ] (A = 600 Bq 600 nucleus decay per 1 second) EC photons SPECT X-ray ( 111 In) γ photons ( 99m Tc) SPECT DIAGNOSTIC The amount of activity used for nuclear medicine: Diagnostic hundreds MBq (1 MBq = 10 6 Bq) Therapy a few GBq (1 GBq = 10 9 Bq) The traditional unit: Ci = Curie (= 1 gram 226 Ra), 1 mci = 37 MBq Physical half-life time (T f1/2 ) Physical half-life time (T f1/2 ) = time required for it to decay to 50% of its initial activity level. = time required for it to decay to 50% of its initial activity level. DIAGNOSTIC THERAPY SPECT PET 99m Tc 6 h 18 F 110 min 131 I 8 d 123 I 13,2 h 11 C 20 min 90 Y 64 h 111 In 2,8 d 13 N 10 min 186 Re 3,7 d 81m Kr 13 s 15 O 122 s 177 Lu 6,6 d number of half-life times Measurement of Radiation Exposure physical quantity: ABSORBED DOSE (D), [Gy] derived quantities: EQUIVALENT DOSE (H T ), [Sv] EFFECTIVE DOSE (E), [Sv] Measurement of Radiation Exposure ABSORBED DOSE (D), [Gy] Measure of energy deposition (E) per unit mass (m) in ANY medium by ANY type of radiation: D = E / m Unit: 1 Gy (gray) = 1 J/kg NOTE: > 4000 Gy to raise the temperature of water by 1 0 C The ionization density is very variable from one type of radiation to another and has an important effect on biological sensitivity. DIFFERENT TYPES OF RADIATION: The same absorbed dose biological effects are DIFFERENT 2

3 α LINEAR ENERGY TRANSFER (LET), [ev/m] = mean energy loss per unit track length High LET = α, n 0, p + radiation Low LET = X, γ, β - radiation High LET radiations cause more biologic damage deposit a large amount of energy in a small amount of body tissue per unit dose than low LET. β Measurement of Radiation Exposure EQUIVALENT DOSE (H T ) H T = Σ D T,R. w R Unit: 1 Sv (Sievert) D T,R absorbed dose averaged over the tissue or organ T due to radiation R w R. radiation weighting factor NOTICE: (One Sv is a large dose, annual dose limits are in the order of msv.) Radiation w R photons (γ, X) 1 electrons (all energies) 1 p + 5 α, fusion products 20 Measurement of Radiation Exposure Tissue weighting factors (w T ) w T. tissue weighting factor takes into account different biological sensitivities of each organ to stochastic effects such as cancer H T. equivalent dose EFFECTIVE DOSE (E) E = Σ (D T,R. w R. w T ) E = Σ H T. w T Unit: 1 Sv (Sievert) Tissue or organ w T Gonads 0,20 Red Bone Marrow 0,12 Colon 0,12 Lung 0,12 Stomach 0,12 Breast 0,05 Bladder 0,05 Esophagus 0,05 Liver 0,05 Thyroid 0,05 Skin 0,01 Bone surface 0,01 Remainder Tissues 0,05 TOTAL 1,00 most radiosensitive least radiosensitive Remainder Tissues = adrenals, brain, upper large intestine, small intestine, kidney, muscle, pankreas, spleen, thymus and uterus. Equivalent dose (H T ) x Effective dose (E) Equivalent dose (H T ) = determine dose absorbed by a specific organ or body part, Effective dose (E) = determine effect on the whole body. BASIC PRINCIPLES OF RADIATION BIOLOGY E = Σ H T. w T Tissue or organ H T w T Lung tissue 5,0 msv 0,12 Liver 1,5 msv 0,05 Ribs 1,0 msv 0,12 Ovaries 0,15 msv 0,2 E = (5x0,12) + (1,5x0,05) + (1x0,12) + (0,15x0,2) = 0,825 msv 3

4 All biological damage effects begin with the consequence of radiation interactions with the atoms forming the cells. Interaction radiation with matter = ionization IONIZATION Ionizing radiation interacts only with atoms by a process called ionization. Direct effects DNA molecule Indirect effects Energy transferred to e - exceeds the binding energy of electron Electron is ejected from the atom. The result of ionization is an ion pair. Direct effect Radiation interacts with the atoms of the DNA molecule (single or double strand breaks) Radiation interacts with water molecules to form free radicals (this cause damage the DNA) CELL DEATH REPLACEMENT CELLS DETERMINISTIC EFFECTS NO HARM SEVERITY OF EFFECT STOCHASTIC EFFECTS RISK DNA DAMAGE MUTATED CELLS CELL REPARATIVE MECHANISM STOCHASTIC EFFECTS IMMUNE MECHANISM OF THE ORGANISM NO HARM SOMATIC GENETIC NO HARM THRESHOLD dose threshold exists the greater the dose - the greater the effect. the effect occurs shortly after radiation (several days or weeks) specific clinical manifestation DOSE D no dose threshold linear model the higher the dose, the higher risks of biological effect late effects (several years decades) cannot distinguish from spontaneous cases DOSE D THE WHOLE BODY IRRADIATION ACUTE RADIATION SYNDROME The whole body is irradiated with a single D > 1Gy. Hematopoietic: D 1-10 Gy nausea, vomiting, diarrhea, lower white blood cell counts. Gastrointestinal: D 10 to 20 Gy Cardiovascular: D 20 to 50 Gy, Neurovascular: D > 50 Gy TISSUE SKIN LOCAL IRRADIATION EFFECT erythema DOSE THRESHOLD 3 5 Gy necrosis 5 EYE LENS cataract 5 OVARIES TESTICLES EMBRYO/ FETUS permanent sterility temporary sterility permanent sterility mental retardation 2,5 6 0,5-2 3,5-6 0,2 LOCAL IRRADIATION Most often during radiation accidents with external radiation source in industrial radiography ( 192 Ir) Portable radiography devices are often used with little training and poor radiation protection. Dose threshold: D > 3 Gy. SKIN IRRADIATION 4

5 LOCAL IRRADIATION RADIATION EFFECTS IN UTERO The embryo is extremely sensitive to ionizing radiation. Threshold for malformations mgy. D =100 mgy are not reached with diagnostic NM or X-ray examinations (even with 3 pelvic CT scans) These levels can be reached with fluoroscopically guided interventional procedures of the pelvis and with radiotherapy. GESTATIONAL AGE 0-9 days 10 days - 6 weeks 6 weeks - 40 weeks Effects of radiation according to gestational stage STAGE Early embryo (preimplantation) Late embryo (major organogenesis) Fetus (minor organogenesis) RADIOGENIC EFFECTS All-or-nothing response Congenital anomalies, growth retardation Growth and mental retardation, microcephly The radiation effects vary depending on: the gestation age, the dose, and also the dose rate. Biological effect after application of radiopharmaceuticals CAN NOT OCCUR IN DIAGNOSTIC EXAMINATIONS the threshold is over 1 Sv, exposure - effective doses: 1 20 msv (most diagnostic examinations in nuclear medicine involve effective doses of less than 10 msv) MAY OCCUR IN THERAPY after application 131 I during therapy of thyroid carcinoma acute Radiation Syndromes hematopoietic form (nausea, lower white blood cell counts. ) STOCHASTIC EFFECTS Linear no-threshold model from D>100 msv reliable data (Hisoshima & Nagasaki, etc.) Other models: A = model with threshold (- - -) B = hormesis (.) C = supra-linear model (- - -) Despite its limitations, the linear relationship has a useful regulatory role because it provides an easy and effective framework for radiation protection. 2-3x greater risk for children higher rate of cell division higher chance of surviving the latency period of cancer induction. greater risk for young girl and woman 5-10x lower for elderly (> 50 year) STOCHASTIC EFFECTS Radiation risk varies with age and sex: Risk is non-preventable even at low doses. Therefore, the risk of stochastic effects is minimized by lowering the exposure. annual effective dose from background radiation: msv/year Population Working Population STOCHASTIC EFFECTS The annual risk of fatality from cancer: Whole Populatin (including young..) It is extra risk! Low Dose, Low Dose Rate 4 x 10-2 (0,04) per Sv 5 x 10-2 (0,05) per Sv 5

6 Example of application of the risk factor The annual risk of fatality from cancer: Population Working Population Low Dose, Low Dose Rate 4 x 10-2 per Sv Whole Population (including young..) 5 x 10-2 per Sv Cancer accounts for ~ 20% of all deaths in developed nations. RADIATION PROTECTION Medical technologist receive 2,5 msv/year for 20 years. The lifetime dose: 20 years x 2,5 msv = 50 msv = 0,05 Sv The risk of cancer is 4 x 10-2 x 0,05 = 0,002 (0,2%) The risk of fatal cancer (due to radiation) for this individual has increased from 20% to 20,2%. GOALS OF RADIATION PROTECTION ELIMINITE deterministic effects REDUCE incidence of stochastic effects PRINCIPLES OF RADIATION PROTECTION 1. SECURITY RESOURCES In the Nuclear Medicine department exists controlled area: restricted access must be clearly marked with radiation warning signs pregnant not allowed to enter Security resources Justification Optimization Dose Limitation in controlled areas persons may receive an effective dose of more than 6 msv/year: room for preparation and administration of radiopharmaceuticals PET imaging room room for storage of radioactive waste 2. JUSTIFICATION No unnecessary use of radiation is permitted, which means that the advantages (benefit) MUST OUTWEIGH the disadvantages (risk). 3. OPTIMIZATION Radiation doses should all be kept as low as reasonably achievable = ALARA approach. ALARA As Low As Reasonably Achievable balance between administered ACTIVITY (and thus patient radiation dose) and IMAGE QUALITY Diagnostic benefit Risk of medical exposure 6

7 OPTIMIZATION IN NUCLEAR MEDICINE OPTIMIZATION IN NUCLEAR MEDICINE ADMINISTERED ACTIVITY [MBq] HIGH ACTIVITY = HIGH PATIENT RADIATION DOSE DIAGNOSTIC REFERENCE LEVEL OPTIMAL VALUES OF ACTIVITY SUFFICIENT IMAGE QUALITY WHILE THE LOWEST PATIENT RADIATION DOSE LOW ACTIVITY = LOW IMAGE QUALITY Optimal activity for adults is based on diagnostic reference level (DRL) = A for patient weight m=70 kg, (in routine clinical practice should not be exceeded) PUBLIC OCCUPATIONAL STUDENTS (16-18 let) 4. DOSE LIMIT (per year) EFECTIVE DOSE (E) 1 msv/1 year, 5 msv/5 years 50 msv/1 year, 100 msv/5 years EQUIVALENT DOSE (H T ) lens of the eye 1 cm 2 skin 15 msv 50 msv extremities 150 msv 500 msv 500 msv 6 msv 50 msv 150 msv 150 msv RADIATION PROTECTION IN NUCLEAR MEDICINE AGAINST EXTERNAL EXPOSURES AGAINST INTERNAL EXPOSURE DOSE LIMIT OF: H T - preventing deterministic effects. E - minimizing the potential risks of stochastic biological effects. MEDICAL EXPOSURE IS NOT COUNTED IN DOSE LIMIT!!! TIME Radiation protection minimize the amount of time during the exposure DISTANCE AGAINST EXTERNAL EXPOSURES maximize the distance from the radiation source Inverse square law (1/r 2 ) = if the distance is doubled, the exposure is 4x reduced. Effect of Shielding use proper and sufficient shielding: Alfa almost anything (even a sheet of paper) Betas low atomic-number materials (plastic) Gamma/X-ray dense (heavy) materials (lead, concrete). SHIELDING utilize shieling to avoid direct exposure to the radiation source 7

8 Radiation protection AGAINST INTERNAL EXPOSURE E 50 msv/y Max. dose limit per year for radiation workers Do not eat, drink, smoke or chew gum in controlled area. Wear protective clothing, such as gloves or respirators. Preparing RF in special lab. 10 msv/y Radioactive Thorium Beach In Guarapari, Brasil 9 msv/y Exposure by airline crew flying the New York Tokyo polar route 6,1 msv PET exam 18F-FDG (320 MBq) 3 msv/y 2 msv/y Natural radiation in the CR Air crew 0,05 msv Chest X-ray image 8