Nuclear Medicine: Radionuclides, Radiopharmaceuticals and Radiation Protection

1. Nuclear Medicine: Radionuclides, Radiopharmaceuticals and Radiation Protection Katrina Cockburn, Nuclear Medicine Physicist

2. What is Nuclear Medicine • “Diagnostic imaging” • “Radiotherapy” • “Diagnostic testing” • “Make people glow in the dark” • Or… “Nurse”

3. What makes us different from: • X-Ray? • Linac Radiotherapy? Function

4. 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

5. 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

6. NORMAL BRAIN CT

7. BRAIN CT THIS IMAGE WAS ACQUIRED POST-MORTEM

8. Why is this useful?

9. 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

10. 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

11. Why is this useful? • Additional value of PET-CT in the staging of lung cancer: De Wever et al, 2007. 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%

12. Components of NM Procedures Radiopharmaceutical Detection Device Analysis

13. 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

14. 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

15. 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 The Ideal Radiopharmaceutical • Easy to prepare • Labelling Stability

16. 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

17. Commonly Used Radionuclides * Annihilation photons produced in pairs

18. Radionuclide Generators • Solution to the problem of supply of short-lived radionuclides (e.g. Tc99m, Rb82) • Principle: Relatively long lived parent radionuclide Decay Daughter radionuclide with shorter half-life

19. Elution • Remove ‘daughter’ radionuclide • No removal of ‘parent’ radionuclide • Sterile • Techniques • Precipitation • Distillation • Ion exchange • + Others

20. Mo99 Decay Scheme Mo99 (T½ = 67h) β- (91.4%) Tc99m (T½ = 6h) β- (8.6%) γ Tc99 (T½ = 2.1x105 years) β- Ru99 (stable)

21. Ion Exchange One-way air filter Mo99 Absorbed onto Alumina Evacuated Vial Filter Eluent Reservoir Lead/ Depleted Uranium Shield Na+(TcO4)- Na+Cl- Generator

22. Tc99m Generator Mo99 Transient Equilibrium Tc99m

23. Tc99m Generator with Elution Mo99 Tc99m

24. 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

25. 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

26. Fluorine – 18 9 protons, 9 neutrons Nuclear Reaction for F-18 proton Oxygen -18 8 protons, 10 neutrons neutron • Proton fired at oxygen-18 • O-18 absorbs the proton • Temporary creation of fluorine-19 • Emission of neutron • Creation of fluorine-18

27. 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

28. Diagram of a cyclotron

29. ABT Desk-top cyclotron

30. Radiopharmacy QA • Radionuclide Purity • Mo99 ‘Breakthrough’ • Aluminium • Other Radioactive contaminants • (fission impurities) • Radiochemical Purity • Free Tc99m • Different bio-distribution • Unnecessary radiation of organs • Misdiagnosis • Sterility • Aseptic techniques • Routine monitoring for microbiological, particulate, and radioactive contamination } first eluate from each generator Quality guaranteed by manufacturer } • First vial of new batch for commercial kits • All kits for unlicensed products

31. 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

32. Factors Affecting the Dose • Administered Activity • Diagnostic Reference Levels (ARSAC) • Effective Half-Life • Bio-Distribution • Radiochemical purity • Pathology • Drugs • Type of radioactive decay • Energy of emissions

33. Patient Dosimetry • The Cumulated Activity: Ãs • The activity of the radiopharmaceutical within a given organ integrated over time • Depends on the effective half life

34. 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

35. Patient Dosimetry • Dose to the target organ, Dt • Takes into account dose from activity within the target organ and all other organs

36. Patient Dosimetry • Need to account for differing radiosensitivities: • Use ICRP weighting factors for different organs to get the Effective Dose, H

37. Radiopharmaceuticals and doses

38. Protection of the PatientIR(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

39. Protection of the PatientMARS 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

40. 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

41. 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

42. 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

43. 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

44. Radiation ProtectionIRR • 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

45. Radiation protection from patientsIRR • 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

46. 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

47. 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

48. Transport of Radioactive Materials • Controlled under Carriage of Dangerous Goods 2009 • Drivers need to be trained • Vehicles need to be marked • Emergency kits andinstructions