1. Application of Radioisotopes in Diagnosis and Treatment of Diseases: Presenter: John Pemba Radiopharmacist Nuclear Medicine Unit BMC

2. Presentation outline: Definition of terms Overview Mechanism of action Use in diagnosis Use in the treatment of various disease conditions Adverse reactions Advantages and disadvantages of radioisotopes Radiation safety precautions Conclusion & remarks

3. Definitions of key terminologies Radioisotopes(radioactive isotopes): - These are atoms of the same element which have the same number of protons but different number of neutrons Radiopharmaceutical: – Is a drug that is composed of a radioisotope bond to an organic molecule. – The organic molecule conveys the radioisotope to specific organs, tissues or cells.

4. Definition cont…. Radioactive decay – Is the process of shedding off the excess radioactive energy – Atoms regain stability by shedding radioactive energy – The radioactive decay process of each type of radioisotope is unique and is measured with a time period called a half-life (t 1/2 )

5. Sources of radiations:

6. Radioactive Decay

7. Properties of radiations α – particles(alpha): – Have 2 protons and 2 neutrons(mass number of 4) – Have a charge of +2 – Slow and heavy – Have low penetrating power – Travel few centimeters in air – Can be stopped by a sheet of paper or gloves – Ionize other atoms strongly

8. Properties of radiations β -particles (Beta) – Have a charge of -1 – Mass of 1/2000 of proton (same as electron) – They are fast – Medium penetrating power – Can be stopped by aluminium sheet or plastic – Ionize atoms that they pass through

9. Properties of radiations γ – radiations(Gamma): – Are electromagnetic waves (not particles) – Have no mass, no charge – Have high penetrating power – Prevented by thick sheet of metal or concrete – Do not directly ionize atoms but indirectly (free radicals)

11. 1.Diagnostic radiopharmaceuticals ► Commonly used Radioisotope is : Technetium-99m (Tc- 99m) – Element number 43, Group VIIB in Periodic table – Does not occur naturally – Heavy metal (transition element)

13. Technetium-99m ► Tc-99m obtained from generator ► Eluate: NaTc0 4 - = Na + + TcO 4 - ► Oxidation state is +7 ► T 1/2 is 6 hours ► The size and charge of TcO 4 - is similar to ClO 4 - and I - ► Hence ; Biodistribution is similar: thyroid, gut, kidneys etc.

14. Technetium-99m  IV Administration – Clearance from blood is multi-exponential – Diffusion to interstitial space – Active uptake in organs (slow) – 75% pertechnetate is protein bound  Biodistribution Stomach, thyroid, salivary glands, intestines, sweat glands, choroid plexus, kidney, mucous membranes.

15. Tc-99m Radiopharmaceuticals ► Tc99m-pertechnetate :Used to study:pertechnetate – Thyroid uptake and thyroid imaging Thyroid – Stomach and salivary gland imaging Meckel's diverticulum imaging Meckel's diverticulum – Brain imaging – Micturating cystogram – First pass blood flow imaging – First pass peripheral vascular imaging – Lacrimal imaging

16. Tc-99m Radiopharmaceuticals ► Tc99m-Human albuminHuman albumin – Cardiac blood pool imaging – Peripheral vascular imaging ► Tc99m-Human albumin macro aggregatesHuman albumin – Lung perfusion imaging ► Tc99m-Phosphonates and phosphates (MDP) – Bone imaging – Myocardial imaging

17. Tc-99m Radiopharmaceuticals ► Tc99m-DTPA (diethylenetriaminepenta-acetic acid)DTPA – Renal imaging – First pass blood flow studies – Brain imaging – Lung ventilation imaging

18. Tc-99m Radiopharmaceuticals ► Tc99m-DMSA(III) (dimercaptosuccinic acid)dimercaptosuccinic acid – Renal imaging ► Tc99m-Colloid – Bone marrow imaging – GI Bleeding – Lymph node imaging – Esophageal transit and – reflux imaging – Lacrimal imaging

19. Tc-99m Radiopharmaceuticals ► Tc-99m-Red blood cells (RBC) – Red cell volume – GI bleeding – Peripheral vascular imaging – Cardiac blood pool imaging ► Tc99m-Exametazime (HMPAO) – Brain imaging

20. Dual Head Gamma Camera for SPECT Imaging

21. Thyroid scan/ imaging Can obtain image of the thyroid gland using Iodine 125, Iodine 131, Tc-99m

22. Indications of Endocrine Nuclear Medicine Determination of thyroid size, function, and position. Evaluation of functional status of thyroid nodules. Evaluation of thyroid and neck masses. Evaluation of patients with history of head and neck irradiation. Quantitative thyroid uptake (I-131 uptake).

23. Indications…. Detection of ectopic thyroid tissues such as substernal or sublingual locations of thyroid tissue (I-123). Detection of thyroid metastases and assessment of response to therapy (I-131

27. Skeletal imaging Various radiopharmaceuticals are used for detection of bone fractures, infections, metastases etc. – Tc-99m/MDP, Pyrophosphate, Medronate used.

28. Osteogene sarkoom (twee verskillende pasiënte)

29. Infection Imaging Radiopharmaceuticals used include: – Ga-67 citrate – Tc-99m WBCs

31. Perinephric abscess Labelled white cell study Ga-67 study

32. Lung scanning Radiopharmaceuticals for detection of various diseases of the lungs (TB, Cancer, etc) – Tc-99m DTPA (as aerosol) – Kr-81m (gas) – Xe-133 (gas) – Xe -127 (gas)

34. Renography Radiopharmaceuticals for renogram include: – Tc-99m DMSA – Tc-99m DTPA – Tc-99m MAG3

36. Posterior opnames Beelde een minuut elk Dïuretikum na 18 minute Dïurese Renogram L R

37. Myocardial perfusion imaging Radiopharmaceuticals used : – Tc-99m MIBI – Tc-99m Tetrofosmin – Tc-99m Mebrofenin – Tl -201

38. MPI: Ischemia

39. 2. Radiotherapy

40. RadionuclideHalf-lifeMode of decayE βmax (keV) 90 Y64.00 hβ-β- 2280.1 131 I8.02 d β -,  970.8 153 Sm46.28 h β -,  808.4 89 Sr50.53 dβ-β- 1496.6 177 Lu6.73 d β -,  498.3 188 Re16.98 h β -,  2120.4 186 Re3.72 d β-, β-,  1069.5 32 P14.26 d β-β- 1709.0

41. Radiotherapy…. Radioisotopes targeted to specific areas of the body where cancer is present. Radiation emitted from the isotope kills cancer cells.isotope These isotopes have short half-lives, meaning that most of the radiation is gone within a few days or weeks.

44. RadionuclideHalf-lifeMode of decayEnergy (keV) 211 At7.2 h α 6790 212/213 Bi60/46 min α 8320 225 Ac10.0 d α 5750 223 Ra11.43 d α 5780

45. Radium-223 Chloride Radium-223 Chloride

46. 131 I-MIBG 131 I-MIBG Yttrium-90 Yttrium-90 Lutetium-177 DOTATOC Lutetium-177 DOTATOC

47. Yttrium-90 Ibritumomab Yttrium-90 Ibritumomab Yttrium-90 Zevalin Yttrium-90 Zevalin 131 I-Tositumomab (Bexxar ® ) 131 I-Tositumomab (Bexxar ® ) 131 I-Rituximab 131 I-Rituximab

49. 131 I-Lipiodol 90 Y-TeraSphere 90 y-microspheres 90 y-microspheres

50. Advantages of radioisotopes in medicine Identify abnormalities very early in the progression of the disease often before medical problems are apparent with other diagnostic tests.

51. Advantages Gamma radiations e.g. from Cobalt -60 used in the diagnosis and treatment of thyroids, is more effective than other methods like chemotherapy The P32 and the I-123 are ideal in the treatment and diagnosis of leukemia and tumors, detecting this early by the use of radioisotopes helps in early medical treatments and interventions

52. Advantages Cost effective when used in research. Cost effective and does not cause harm when used to sterilize medical equipment

53. Disadvantages of radioisotopes in nuclear medicine Negative impact on health if not handled properly. May cause nausea, skin burns, leukemia and lung cancer, mutations, and may lead to death Radioisotopes are expensive and not every hospital can pay the price for consuming them(initial investment) They are also inevitably hard to store since they continuously emit radiation

54. Disadvantages The radioactive waste disposal needs special methods and containers Transportation and handling require special training and licensure (limitation)

55. COMPARISON OF RISKS

56. Precautions for Radiation exposure ALARA PHILOSOPHY o Regulations require that its licensees maintain occupational exposures As Low As Reasonably Achievable (ALARA) TDS rule: o Time- spend as shorter time as possible Distance- keep distance with radiations Shielding- always work under shield

57. Conclusions Regarding Health Risk Bottom line the fact is that any radiation exposure, no matter how small, carries with it some risk. However, it is well known that on average these risks are comparable to or smaller than risks we encounter in other activities or occupations that we consider safe, so long as laid down precaution regulations are followed

58. Concluding remarks Since we have extensive control over how much radiation exposure we receive on the job, we can control and minimize this risk. The best approach is to keep our dose As Low As Reasonably Achievable (ALARA).

59. Thank you !