1. 3 rd year Inorganic Pharmaceutical Chemistry College of Pharmacy

2. The Nature of Radioactivity Chemical versus nuclear stability Important Terms Isotopes Radioisotopes Radiopharmaceuticals Radioactive Decay, half-life

3. Radioactive decay particles 1. Alpha, α (A = 4, Z = +2) 2. Beta, β - (negatron) (n → p + β - ) (Z = -1) and the positron, β + ( p → n + β + ) (Z = + 1) 3. Gamma, γ (β + + e - → 2 γ) (no change in mass or charge) and X-rays through K-capture

4. Kinetics of isotope decay -dA/dt = λA ……………………………….…………(1) Where -dA/dt is the rate of radioactive decay of a radioisotope with an activity A and λ is a constant. Rearranging equation 1 and integration with respect to t leads to the equation log A = log A o - 0.301 (t/t 1/2 ) Where A o is the initial radioactivity and t 1/2 is the half-life of the isotope.

5. Radiation Dosimetry There are two areas of concern in radiological health standards that require description and units of measurement. They are exposure dose ( amount of radiation available for interaction with some target material and measured in roentgen, r = 1.610 x 10 12 ion pairs per gram of air and rhm means roentgens per hour at distance of 1m from source) and absorbed dose measured in rad which is equal to 100ergs of energy absorbed by 1g of material. The rem is commonly used to determine doses received by those working with radioisotopes.

6. Radiation Exposure The radioactivity from a particular source is inversely proportional to the square of the d distance from the source. For example if a sample radiating 5.0x10 4 rads at 10cm. The radiation at 50cm, x, can be calculated as follows: 5.0x10 4 /x = 50 2 / 10 2 x = 200 rads

7. Biological Effects of Radiation The effect of radioactivity on biological tissues depends on a number of factors: 1.Penetration 2.Energy of radiation 3.The particular tissue and the surface area exposed 4.The dose rate of the radiation.

8. Effect of Radiation on Tissues Radiations cause ionization in tissue molecules producing ions and /or free radicals. These species can alter the local pH or serve to initiate free radical chain reactions resulting in the production of peroxides or other toxic compounds. These and other events can create a hostile environment for tissue cells, leading to necrosis, and ultimately to complete cell destruction of tissue or organ.

9. Effect of Radiation on Tissues …. The production of a variety of potentially toxic species which can alter the DNA in cells and cause cross linking between certain amino acids in proteins. Lipoproteins are also oxidised by free radicals. Radioactive xH 2 O → xH. + xHO. → other products particles ↓ ↓ yH 2 yH 2 O 2

10. Instrumentation The main instruments used for monitoring radiation dosage are GM counters which is usually used for monitoring work areas. Other detectors are also worn or carried out by individuals to aid in maintaining personal records e.g. film badges and pocket monitors.

11. Protection The usual shielding materials are lead and concrete. The half-thickness is the thickness of material that is needed to reduce the amount of radiation from a particular source by one half.

12. Internal Administration of Radioisotopes There are a number of preparations containing radioisotopes which are used internally for therapeutic and diagnostic purposes. These preparations are referred to collectively as radiopharmaceuticals. Isotopes important as radiopharmaceuticals are gamma or beta emitters. Radioisotopes are concentrated at certain tissues e.g. 131 I in the thyroid gland. Areas of heavy concentration are referred to as “hot spots’ while areas where concentration is light are known as “cold spots”. Tags are used to incorporate isotopes and direct them to particular tissues.

13. Internal Administration of Radioisotopes……. Selective absorption and distribution are important factors to be considered in their use. Energy of the isotope is an important factor in selecting radiopharmaceuticals. Low energy will not penetrate tissues hence cannot be detected while high energy will cause unnecessary damage to surrounding tissues. The duration of an isotope in the body is determined by two time factors, the physical and the biological half-lives as in the equation t eff = t 1/2 t b / (t 1/2 + t b )

14. Internal Administration of Radioisotopes……. Normally the administration of radioisotope takes short time, few minutes. Administration of isotopes can be orally or intravenously, for diagnostic or therapeutic purposes. Other methods of applying radioisotopes include teletherapy, implantation therapy and contact therapy.

15. Advantages The importance of radiochemical techniques are invaluable in biological studies since; * One can make measurements at very low concentrations * One can avoid complex extraction procedures * Radiochemical versions of biological molecules follow exactly the same reaction as non-radioactive ones, so metabolic pathways can be determined precisely * One can produce pictures of the distribution of radioactivity in tissues and even whole organism to show the location of particular molecules in cells and organs.

16. Disadvantages * Hazards of overuse of radioactive active materials. * Sophisticated equipment and skill are needed.

17. Internal Administration of Radioisotopes Radiopharmaceuticals are preparations containing radioisotopes which are used internally for diagnostic or therapeutic purposes. The main features of isotopes are β or γ– emitters. β is usually the negatron rather than the positron.

18. Internal Administration of Radioisotopes Areas of heavy concentration are called “hot spots” while areas where concentration is light are called “ cold spots” Isotopes may be “tagged” to a molecule which aids in directing it to a particular tissue with some degree of specificity. The isotopes and their decay products should be of low toxicity The isotopes should be able to be eliminated from the body easily. This will reduce potential hazards of radiation.

19. Internal Administration of Radioisotopes For diagnostic procedures isotopes should have sufficient energy to be monitored outside the body normally by Autoradiography – exposing a photographic plate over the appropriate area of the body. Hot and cold spots may indicate possible tumor sites or areas of abnormal activity.

20. Radiation Detection Scintillation scanning – based on the ability of ionising to excite certain molecules to higher electronic states. The emitted light will be shifted to the wave length of the PM tube. GM tubes – detect radiation based on the measurement of ionisations produced in the gas within the tube. Therapeutic isotopes are used for their destructive effects on tissue. The radioactivity should not spread to surrounding tissues. This is difficult to control.

21. Internal Administration of Radiopharmaceuticals For diagnostic or therapeutic purposes, the internal administration of radioisotopes is usually orally or intravenously. Teletherapy involves directly focusing gamma- emitting isotopes with activity as high as 2000c on the area under treatment.

22. More Techniques Implantation therapy or interstitial irradiation describes various procedures involving direct introduction of sealed radioactive sources in the form of encapsulated seeds, needles or wires are implanted into tumor tissues. Contact therapy uses applicators containing beta emitters as dermatological or ophthalmic tumors. This dosage can be removed as and placed where desired.

23. Radiation Detection The most widely used methods of detecting radioactivity for diagnostic procedures are the GM counters, scintillation counters, radiography and Gamma Cameras. 1. Autoradiography involves the exposure of a photographic plate over the area under investigation. The picture may show areas of varying concentrations of the radioisotopes termed as 'hot' spots, more likely tumor sites or areas of abnormal activity.

24. Scintillation Counting 2. Scintillation counting involves the ability of gamma or beta to cause excitations in molecules to higher electronic levels. When these molecules return to their ground states energy is released and then shifted to lower energies to match that of the photomultiplier tubes, 420nm.

25. GM Tubes and Gamma Cameras 3. GM tubes are used to detect and measure radiation from diagnostic isotopes by measuring the ionisation it produces. 4. Gamma cameras are used mainly for whole body examination. Large sodium iodide crystals and large number of photomultiplier tubes are used to form a picture of organs of interest and compared with stored information for normal organ activities.

26. Technitium-99m Tchnitium is an artificial element produced by the neutron bombardment of molibdinum-98 to produce radioactive molibdinum-99 with the release of gamma rays. Molibdinum-99 decays with a half-life of 67 days to produce echnetium-99m with the release of beta and gamma ray. Technetium-99m decays to the relatively stable technetium-99 with a half-life of 6 hours with the release of gamma rays.

27. Technitium-99m Advantages of Technitum-99m compared to other radioisotopes It has a short half-life, 6hourrs. It is a single gamma emitter. It is carrier free. It is suitable for brain scanning.

28. Technitium-99m Techniutium is eluted from the nuclear generator as sodium pertechnitate using sodium chloride. The rate of absorption of sodium technitate is similar to that of iodide hence care must be taken on using it for thyroid scan. Technitium sulfide is a colloidal mixture absorbed by the reticuloendothelial cells lining the liver, spleen and bone marrow. It offers a better choice than gold-98 for the scanning of these organs.

29. Thank You