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Nuclear Medicine: Radionuclides, Radiopharmaceuticals and Radiation Protection Katrina Cockburn, Nuclear Medicine Physicist What is Nuclear Medicine “Diagnostic imaging” “Radiotherapy” “Diagnostic testing” “Make people glow in the dark” Or… “Nurse” What makes us different from: X-Ray? Linac Radiotherapy? Function What is Nuclear Medicine? a medical imaging technique in which a pharmaceutical, labelled with a radioactive substance, is administered to the patient. The amount of radioactivity in various parts of the body is then measured with a gamma camera Why is this useful? Any imaging modality can show what is there We use the body’s own physiology to indicate and/or treat abnormalities which would not be possible using conventional radiology or radiotherapy NORMAL BRAIN CT BRAIN CT THIS IMAGE WAS ACQUIRED POST-MORTEM Why is this useful? Why is this useful? •CT stage T3 No Mo •PET/CT stage T3 N2 Mo Lymph Node <10mm Images courtesy of Institute of Nuclear Medicine, University College London Why is this useful? •CT staging T4 N2 Mo •PET/CT staging T4 No Mo Images courtesy of Institute of Nuclear Medicine, University College London Why is this useful? Additional value of PET-CT in the staging of lung cancer: De Wever et al, 2007. Tumour Node Met TNM PET CT 86% 80% 98% 70% CT 68% 66% 88% 46% PET 46% 70% 96% 30% Co-Read 72% 68% 96% 54% Over-staging: PET-CT T=8%, N=16%, CT T=16%, N=20% Under-Staging: PET-CT T=6%, N=4%, CT T=12%, N=6% Components of NM Procedures Radiopharmaceutical Detection Device Analysis Radiopharmaceutical Two functions: Pharmaceutical – acts as tracer Radioactive material – allows us to monitor distribution Both functions may be performed by the radioactive isotope I-123 thyroid imaging Or isotope may need to be chemically bound to a pharmaceutical Tc99m – HDP for bone scans Properties of Radioactive Materials May emit x-rays, gamma-rays, electrons or alpha particles There may be one or more of these emitted Daughter products may also be radioactive Gamma rays will have “characteristic” energies Decay exponentially The Ideal Radiopharmaceutical Pharmaceutical Short biological half-life Localise only in the area of interest Should not alter physiological system under examination Minimal/No side effects Radionuclide Short physical half-life Pure Gamma Emitter Energy 100-200keV Suitable for incorporation into a pharmaceutical Readily available Easy to prepare Labelling Stability Mechanisms of Localisation In-Vivo Active Cellular Transport potassium analogues in myocardial imaging Simple diffusion Kr-81m in lung ventilation Capillary Blockade Tc99m-MAA for lung perfusion Physiochemical adsorption Phosphates localising in mineral phase of bone Antibodies Labelled antibodies for tumour imaging Commonly Used Radionuclides Radionuclide Production Half-Life Generator Photon Energy (keV) 140 Tc99m Tl201 Cyclotron 68-80 (x-rays) 74h I123 Cyclotron 160 13h In111 Cyclotron 173, 247 67h F18 Cyclotron 511* 110 min Rb82 Generator 511* 75 sec I131 Reactor 280, 360, 640 8 days * Annihilation photons produced in pairs 6h Radionuclide Generators Solution to the problem of supply of shortlived radionuclides (e.g. Tc99m, Rb82) Principle: Relatively long lived parent radionuclide Decay Daughter radionuclide with shorter half-life Elution Remove ‘daughter’ radionuclide No removal of ‘parent’ radionuclide Sterile Techniques Precipitation Distillation Ion exchange + Others Mo99 Decay Scheme Mo99 (T½ = 67h) - β (91.4%) Tc99m (T½ = 6h) - β (8.6%) γ Tc99 (T½ = 2.1x105 years) β - Ru99 (stable) Ion Exchange One-way air filter Mo99 Absorbed onto Alumina Evacuated Vial Filter Eluent Reservoir Na+Cl- Generator Lead/ Depleted Uranium Shield Na+(TcO4)- Tc99m Generator 120 Mo99 100 Activity 80 60 40 Tc99m Transient Equilibrium 20 0 0 24 48 72 96 120 144 168 192 Time (Hours) Tc99m Generator with Elution 120 Mo99 100 Activity 80 60 40 Tc99m 20 0 0 24 48 72 96 120 Time (Hours) 144 168 192 Radio-Labelling with Tc99m Cold Kits Pre-packed set of sterile ingredients designed for the preparation of a specific radiopharmaceutical Typical Ingredients Compound to be complexed to the Tc99m e.g. methylene diphosphonate (MDP) Stannous Ions (Sn+) Stablilsers, buffers, antioxidants, bactericides Cyclotron and PET isotopes Most PET isotopes are produced in cyclotrons F18, C11, O15 Positron emitters have “too many” protons for stability Normally produced by smashing protons into stable targets To make F18, fire protons into O18 enriched water Nuclear Reaction for F-18 proton Oxygen -18 Fluorine – 18 8 protons, 10 neutrons 9 protons, 9 neutrons Proton fired at oxygen-18 O-18 absorbs the proton Temporary creation of fluorine-19 Emission of neutron Creation of fluorine-18 neutron Physics of the cyclotron Charged particles move in circles in a static magnetic field The size of the circle depends on the energy of the particle Electric fields can be used to accelerate particles Cyclotron uses both types of fields to accelerate a beam of protons into a target Diagram of a cyclotron ABT Desk-top cyclotron Radiopharmacy QA Radionuclide Purity } Mo99 ‘Breakthrough’ first eluate from each generator Aluminium Other Radioactive contaminants Quality guaranteed by manufacturer (fission impurities) Radiochemical Purity Free Tc99m Different bio-distribution Unnecessary radiation of organs Misdiagnosis } First vial of new batch for commercial kits All kits for unlicensed products Sterility Aseptic techniques Routine monitoring for microbiological, particulate, and radioactive contamination Radionuclide Calibrator Ionisation Chamber Acceptance Testing Check against national or secondary standards Daily QA Long Lived Source Source assayed using several radionuclide settings Geometrical Dependence Factors Affecting the Dose Administered Activity Diagnostic Reference Levels (ARSAC) Effective Half-Life 1 1 1 effective phys biol Bio-Distribution Radiochemical purity Pathology Drugs Type of radioactive decay Energy of emissions Patient Dosimetry The Cumulated Activity: Ãs The activity of the radiopharmaceutical within a given organ integrated over time Depends on the effective half life Patient Dosimetry The “S-Factor”, S Published by MIRD S(t,s) = D f(t,s) / m D = Total energy from the radiation type f(t,s) = the fraction of the energy absorbed by the target organ (t) which is emitted by the source organ (s) m = the mass of the target organ Patient Dosimetry Dose to the target organ, Dt Takes into account dose from activity within the target organ and all other organs Patient Dosimetry Need to account for differing radiosensitivities: Use ICRP weighting factors for different organs to get the Effective Dose, H Radiopharmaceuticals and doses Radiopharmaceutical Route Typical Activity Effective (MBq) Dose (mSV) Clinical Use Tc99m-MDP i.v. 600 3 Bone Imaging Tc-99m-DTPA Inhaled 20 0.1 Lung Ventilation Tc-99m-MAA i.v. 100 1 Lung Perfusion Tl-201 (thallous chloride) i.v. 80 18 Myocardial Perfusion I-131-sodium iodide oral 400 24 Thyroid metastases Tc99m- labelled red cells i.v. 800 8 Cardiac blood pool Tc99m-labelled white cells i.v. 200 3 Localisation of infection Protection of the Patient IR(ME)R Referral Criteria Justification (ARSAC license holder) Patient identification procedures Labelling of syringes/vials Checking of activity prior to administration Protective clothing Thyroid Blocking Conception, Pregnancy, Breast Feeding Protection of the Patient MARS and ARSAC Certification of medical and dental practitioners Certificates last for 5 years Specific to individual practitioner Specific to individual site Named radiopharmaceuticals and uses Notes for Guidance Pregnancy Policy to check for pregnancy in female patients of child bearing age Notices in departments “Please inform technicians if you may be pregnant” Does the risk to the foetus outweigh the risk to the patient from failure to diagnose and treat Clinical benefit to the mother may be of indirect benefit to the unborn child Conception: Advice to Males No evidence that pre-conceptual irradiation of males can cause any abnormality in their offspring* No need to avoid conception for males undergoing routine diagnostic studies Therapeutic administration of long-lived radionuclides (e.g I-131, Sr-89) Possible appearance of larger quantities of such radionuclides in sperm Avoid conception for 4 months *Doll R et al. Nature 1994;367:678-680 Conception: Advice to Females No need to avoid pregnancy after diagnostic procedures using radiopharmaceuticals with a physical half-life <7days* Diagnostic use of Longer Lived Radiopharmaceuticals: Se75 (adrenal imaging): 12 months I131-MIBG (tumour imaging): 2 months I131 (thyroid metastases): 4 months Therapy I131 (≤800 MBq for treatment of thyrotoxicosis): 4 months P32 (≤200 MBq for treatment of polycythemia): 3 months Sr89 (≤150 MBq for treatment of bone metastases): 24 months *ARSAC Notes for Guidance Dec 1998 p25 Breast Feeding Can the test be delayed? Mother to express breast milk prior to test Advise to stop breast feeding for time depending upon radiopharmaceutical Any I131-iodide: STOP 80 MBq Tc99m-MAA: 12 hours 800 MBq Tc99m-DTPA: 0 hours Radiation Protection IRR Time, Distance, Shielding Handling techniques to reduce time Forceps Syringe Shields Contamination Surfaces in rooms to be smooth and non-absorbent Isolators Protective Clothing No eating or drinking in rooms where unsealed sources handled Wash hand basins close to the exit of rooms Routine contamination monitoring Room surfaces and staff leaving controlled areas Radiation protection from patients IRR In general no restrictions or precautions for diagnostics procedures Exceptions: >10MBq In111-WBC, >120MBq In111 Octreotide >200MBq Ga67 citrate, >30MBq I-131 If the work of the patient is radiosensitive Assessment of exposure and contamination risk Therapy Procedures on Wards Contamination Ward staff will be protected if they follow standard hygiene procedures (e.g. gloves/aprons) Handling & storage instruction should bedding/clothing become contaminated Direct Irradiation No special precautions usually required Risk assessment if patient require intensive nursing Keeping & Disposal of Radioactive Substances EPR Certificates for storage and disposal of radioactive materials Properly designed stores Stock Records Reports to be sent to the Environment Agency Solid waste for incineration Solid waste to landfill Aqueous waste to drains Transport of Radioactive Materials Controlled under Carriage of Dangerous Goods 2009 Drivers need to be trained Vehicles need to be marked Emergency kits and instructions