1. RADIOPHARMACEUTICALS

2. ISOTOPES :
Isotopes are atoms of the same element with the same number of protons but different number of neutrons.
The isotopes of a particular element have the same chemical and physical properties.
Examples of isotopes are :
C , C
Isotopes have same atomic number (same proton) but different mass number (different neutrons)

3. TYPES OF ISOTOPES : Two major types of isotopes are found in nature :
stable isotopes and unstable (radioactive) isotopes.
Stable isotopes maintain their elemental integrity and do not decompose to other isotopic or elemental forms. E.g. 12 C
Unstable or radioactive isotopes decompose by emission of nuclear particles (alpha particles, beta particles, gamma rays, x-rays) into other isotopes of the same or different elements. E.g. 14C

4. Radioactive decay particles
When a radioactive isotope decays, it does so with the emission of certain particles or quantities of energy that are characteristic of the particular isotope involved
Major decay particles are
Alpha particles,
Beta particles,
Negatrons (electrons of nuclear origin)
Positrons
Gamma rays,
X-rays.

5. Alpha particles, α
α particles which constitute alpha radiation consists of 2 protons and 2 neutrons.
Characteristics :
a) They are equivalent to the nuclei of helium atoms 4 He 2
b) They are heavy and positively charged (+2).
c) Weight approximately 6.6x10-24 g
d) The particles move at a relatively slow speed, averaging 0.1 the speed of light (3x1010 ) cm/s.
e) Their penetrating power is very low and can be stopped by a sheet of paper or a very thin sheet of aluminium foil.
f) These particles will travel only 3 to 8 cm in air.
g) Energy value, typically 4 Mev.

6. Alpha particles, α
h) α radiation is usually emitted only from elements having atomic numbers greater than 82.
i) The emission of alpha radiation is illustrated below with radium -226 (the radium isotope having a mass number of 226):
Ra ———> Rn α (or He)
The low penetrating power of alpha particles makes isotopes emitting this type of radiation not useful for biological applications because these particles cannot penetrate tissue.

7. Beta particles, β
β radiation is of two types because there are two types of electrons : negative electron (negatron) and positive electron (positron).
The positron is identical with the negatron in all respects except for its charge of +1 instead of -1. It is also known as the antiparticle of the electron.
When these electrons are emitted from radioactive nuclei, they are called β-particles.
Negatrons (β –) are emitted by unstable nuclei having neutrons in excess of protons.
So, a transformation of a neutron to a proton occurs with the emission of beta radiation (β –).

8. Beta particles, β
Elements undergoing this type of transformation will decay to the element having the next highest atomic number.
n ———> p β –
An example of β decay is shown below :
C ———> N β –

9. Beta particles, β
Positrons (β +) are emitted from nuclei having a proton/ neutron ratio above stable limits.
So a proton can be transformed into a neutron, with the emission of beta – radiation (β +)
p ———> n β +
An example of β decay is shown below :
Zn ———> Cu β +
Positrons are not important in biological applications because they are short-lived and undergoes reactions with electrons to produce gamma radiation.
β e – ———> 2 γ

10. Beta particles, β Characteristics:
They have the mass of an electron (approximately 9.1 x g).
They move at a faster velocity.
Their emissions from elements do not alter the atomic mass but changes the atomic number.
They have more penetrating power than alpha particles and can travel from 10 to 15 mm in water or penetrate almost 1-inch thicknesses of aluminium.
Maximum energy is 1.5 Mev and mean energy is 0.6 Mev.
Many isotopes emitting β – have useful biological applications as the radiation will penetrate tissues.

11. Gamma Radiation, γ
Gamma radiation is electromagnetic but α and β radiations are particulate.
It means γ radiation demonstrates both wave and particle properties.
Gamma rays are radiated as discrete packets of energy (quanta). These are also known as photons.

12. Characteristics:
The rays are of a short wavelength and travel at the speed of light.
Since it is of electromagnetic radiation, it has no mass or charge.
They have very high energy (2 Mev).
They have excellent penetrating power and very thick lead or concrete shielding is required to protect against this radiation.

13. Mode of radioactive decay:
Type of Radiation
Alpha particle
Beta particle
Gamma ray
Symbol or
Charge +2 -1
Speed
slow
fast
Very fast
Ionising ability
high
medium
Penetrating power
low
Stopped by:
paper
aluminium
lead

14. Radiation measurement:
The basic unit for quantifying radioactivity (i.e. describes the rate at which the nuclei decay).
Curie (Ci):
Curie (Ci), named for the famed scientist Marie Curie
Curie = 3.7 x atoms disintegrate per second (dps)
Millicurie (mCi) = 3.7 x 107 dps
Microcurie (μCi) = 3.7 x 104 dps
Becquerel (Bq):
A unit of radioactivity. One Becquerel is equal to 1 disintegration per second.

15. Radiopharmaceuticals
Radiopharmaceuticals are medicinal formulations containing radioisotopes which are safe for administration in humans for diagnosis or for therapy. Or
A radioactive drug that can be administered safely to humans for diagnostic and therapeutic purposes.

16. Radionuclide + Pharmaceutical
Radiopharmaceutical products include inorganic compounds, organic compounds, peptides, proteins, monoclonal antibodies and fragments and oligonucleotides labeled with radionuclide with half-lives varying from a few minutes to several days.
Radionuclide + Pharmaceutical

17. Radiopharmaceuticals
Radiopharmaceuticals used in cancer treatment are small, simple substances, containing a radioactive isotope or form of an element.
They are targeted to specific areas of the body where cancer is present.
Radiation emitted from the isotope kills cancer cells.
1717

18. Application of radiopharmaceuticals
Treatment of disease: (therapeutic radiopharmaceuticals)
Chromic phosphate P32 for lung, ovarian, uterine, and prostate cancers
Sodium iodide I 131 for thyroid cancer
Samarium Sm 153 for cancerous bone tissue
Sodium phosphate P 32 for cancerous bone tissue and other types of cancers
Stronium chloride Sr 89 for cancerous bone tissue

19. Chromic phosphate P 32
Chromic phosphate P 32 is a suspension that is delivered through a catheter, or tube, inserted into the sac surrounding the lungs, or into the abdominal or pelvic cavities.
The usual dosage is millicuries for abdominal administration and 10 millicuries for administration to the lung sac.
Chromic phosphate P 32 also may be injected into the ovaries or prostate.

20. Sodium Iodide I 131
Sodium Iodide I 131 is taken by mouth as a capsule or a solution.
The usual dose for treating thyroid cancer is millicuries, depending on age and body size. Doses may be repeated.
Treatment usually requires two to three days of hospitalization. For this therapy to be effective there must be high levels of thyroid-stimulating hormone (TSH, or thyrotropin) in the blood. This hormone can be injected

21. Precautions Before Treatment With Sodium Iodide I 131
Foods containing iodine, such as iodized salt, seafoods, cabbage, kale, or turnips should be avoided for several weeks prior to treatment with sodium iodide I 131.
The iodine in these foods will be taken up by the thyroid, thereby reducing the amount of radioiodide that can be taken up.
Radioplaque agents containing iodine sometimes are used to improve imaging on an x ray. A recent x-ray exam that included such an agent may interfere with the ability of the thyroid to take up radioiodide.

22. Strontium-89/ Samarium Sm 153 lexidronam
Strontium-89 is injected into a vein. The usual dosage is 4 millicuries, depending on age, body size, and blood cell counts. Repeated doses may be required.
The usual dosage of samarium Sm 153 lexidronam is 1 millicurie per kg (0.45 millicurie per lb) of body weight, injected slowly into a vein.
Repeated doses may be necessary. Because samarium Sm 153 lexidronam may accumulate in the bladder, it is important to drink plenty of liquid prior to treatment and to urinate often after treatment. This reduces the irradiation of the bladder.

23. sodium phosphate P 32
The dosage of sodium phosphate P 32 depends on age, body size, blood cell counts, and the type of treatment.
The usual dosages range from 1–5 millicuries. Repeated doses may be required.

24. Precautions After Treatment With Radiopharmaceuticals
Strontium-89, samarium Sm 153 lexidronam, and large total doses of sodium iodide I 131 may temporarily lower the number of white blood cells, which are necessary for fighting infections. The number of blood platelets (important for blood clotting) also may be lowered. Precautions for reducing the risk of infection and bleeding include:
avoiding people with infections
seeking medical help at the first sign of infection or unusual bleeding
avoiding touching the eyes or inside of the nose
avoiding cuts and injuries

25. It is important to drink plenty of liquids and to urinate often after treatment with sodium iodide I 131. This flushes the radioiodide from the body.
To reduce the risk of contaminating the environment or other people, the following procedures should be followed for 48–96 hours after treatment is sodium iodide I 131:
1. avoiding the handling of another person's eating utensils, etc.
2. avoiding close contact with others, especially pregnant women
3. washing hands after using or cleaning the toilet
4. using separate washcloths and towels
5. washing clothes, bed linens, and dishes separately
6. flushing the toilet twice after each use

26. I131 THERAPY PROCEDURES
  Minor therapies of I131 are single doses of 30 mCi or less. Major therapies of I131 are single doses greater than 30 mCi.
Handling Instructions
     All I 131 should be opened under a fume hood prior to administration to a patient to allow for escape of vapor in the vial.
The activity of each dosage shall be measured in a dose calibrator and verified to be within 10% of the prescribed dose.
Since the exposure rate on the outside of the lead pig and shipping box may be quite high, adequate precautions must be taken when transporting sources.

27. Major Therapies
Patients receiving major therapeutic doses of I131 must be admitted to the hospital.
The patient must have a private room and bath.
The room must also be approved by the Radiation Safety Office, taking into consideration areas adjacent to, above, and below where radiation levels must be within certain limits.
Before the dose is administered, the room must be prepared by Radiation Safety.
This involves covering the floor with plastic or absorbent paper
and covering various articles the patient may touch such as
the telephone, TV control, etc.
    

28. Major Therapies
The dose is usually administered with the patient sitting on the edge of the bed. The bedside table should be covered with an absorbent pad. A physicist or technician from Radiation Safety must be present during administration and is responsible for disposing of the waste.
The nursing instruction form contains specific rules for care of the patient by nurses, visitors restrictions, and handling waste, linens, and eating utensils.
    

29. Major Therapies
Patient rooms used for major therapies may not be released for use by other patients until documented surveys by Radiation Safety staff demonstrate that there is no removable contamination in excess of 200 dpm/100 cm2.

30. Therapeutic procedures can usually be divided into two classes:
Treatment with sealed sources, which are mechanically inserted.
Treatment with solutions.
Sealed sources are encapsulated and therefore the risk of contamination is very small
Ex. Radiopharmaceutical Iodine-125 seeds, used to treat prostate cancer.
Ex of radiopharmaceutical solutions, Iodine-131, Strontium-89

31. Radiation Contamination:
There are several types of radiation that can be emitted from radioactive substances.
The basic types of radiation are alpha, beta and gamma.
Radiopharmaceuticals administered to patients are usually either beta or gamma emitting or a combination of both.
Beta radiation doesn't penetrate more than a few millimeters through tissue.
Gamma emitting radioactive materials can penetrate through tissue and therefore pose an external radiation hazards.

32. Radiation Contamination:
There is an important difference between radiation exposure and radioactive contamination.
Radiation exposure of a person can occur at a distance from the radioactive materials or source.
Radiation exposure usually occurs as a result of gamma rays being emitted by the radioactive materials and traveling through air.
Gamma rays that are absorbed by the body can cause harm.

33. Radiation Contamination:
If a person is contaminated it means that the person has come into contact with a radioactive substance and that this material is present on skin, clothing or on objects.
Contamination is hazardous because the radioactive materials can be inhaled or ingested.

34. Production of radionuclides:

35. 1- Charged particle bombardment
Radionuclides may be produced by bombarding target materials with charged particles in particle accelerators such as cyclotrons.
A cyclotron consists of :
Two flat hollow objects called Dees.
The dees are part of an electrical circuit.

36. Cont…
On the other side of the dees are large magnets that (drive) steer the injected charged particles (protons, deutrons, alpha and helium) in a circular path.
The charged particle follows a circular path until the particle has sufficient energy that it passes out of the field and interact with the target nucleus.

37. Cyclotron

39. 2- Neutron bombardment
Radionuclides may be produced by bombarding target materials with neutrons in nuclear reactors.
The majority of radiopharmaceuticals are produced by this process.

41. Difference between Fission & Fusion
Nuclear Fission
Nuclear Fusion
Definition:
Fission is the splitting of a large atom into two or more smaller ones.
Fusion is the fusing of two or more lighter atoms into a larger one.
Natural occurrence of the process:
Fission reaction does not normally occur in nature.
Fusion occurs in stars, such as the sun.
Byproducts of the reaction:
Fission produces many highly radioactive particles.
Few radioactive particles are produced by fusion reaction, but if a fission "trigger" is used, radioactive particles will result from that.
Conditions:
Critical mass of the substance and high-speed neutrons are required.
High density, high temperature environment is required.

42. Nuclear Fission
Nuclear Fusion
Energy Requirement:
Takes little energy to split two atoms in a fission reaction.
Extremely high energy is required to bring two or more protons close enough that nuclear forces overcome their electrostatic repulsion.
Energy Released:
The energy released by fission is a million times greater than that released in chemical reactions, but lower than the energy released by nuclear fusion.
The energy released by fusion is three to four times greater than the energy released by fission.
Nuclear weapon:
One class of nuclear weapon is a fission bomb, also known as an atomic bomb or atom bomb.
One class of nuclear weapon is the hydrogen bomb, which uses a fission reaction to "trigger" a fusion reaction.

43. 3- Radionuclide generator systems
Principle:
A long-lived parent radionuclide is allowed to decay to its short-lived daughter radionuclide and the latter is chemically separated in a physiological solution.
Example:
technetium-99m, obtained from a generator constructed of molybdenum-99 absorbed to an alumina column.

44. A technetium-99m generator is a device used to extract the metastable isotope 99mTc of technetium from a source of decaying molybdenum-99.
99Mo has a half-life of 66 hours
can be easily transported over long distances to hospitals
where its decay product technetium-99m (with a half-life of only 6 hours, inconvenient for transport) is extracted and used for a variety of nuclear medicine diagnostic procedures, where its short half-life is very useful.

45. 99Mo/99mTc Generator:

48. Preparation of Radiopharmaceuticals

49. Compounding: Can be as simple as:
adding a radioactive liquid to a commercially available reagent kit
Can be as complex as:
the creation of a multi-component reagent kit
Kit for radiopharmaceutical preparation
means a sterile and pyrogen-free reaction vial containing the non radioactive chemicals [e.g., complexing agent (ligand), reducing agent, stabilizer, or dispersing agent] that are required to produce a specific radiopharmaceutical after reaction with a radioactive component.

51. Sterilization:
Radiopharmaceutical preparations intended for parenteral administration are sterilized by a suitable method.
Terminal sterilization by autoclaving is recommended for heat stable products.
For heat labile products, the filtration method is recommended.

52. STABILITY OF COMPOUNDED PREPARATIONS
All extemporaneously compounded parenteral radiopharmaceutical preparations should be used no more than 24 hours post compounding process unless data are available to support longer storage.

53. Radiation shielding:
Adequate shielding must be used to protect laboratory personnel from ionizing radiation.

54. Pro-Tec II Syringe Shield
Guard Lock PET Syringe Shield
Pro-Tec V Syringe Shield
Color Coded Vial Shields

55. Vial Shield
Unit Dose Pig
High Density Lead Glass Vial Shield
Sharps Container Shields

56. Radioactive Dating
Radioactivity is often used in determining how old something is, this is known as radioactive dating.
When C-14 is used, the process is called radiocarbon dating
The trick is to use appropriate half-life; for best results, the half- life should be on the order of somewhat smaller than the age of the object.
C-14 is used because all living things take up carbon from the atmosphere, so the proportion of C-14 in the carbon in a living organism is the same as the proportion of the C-14 in the carbon in the atmosphere
For many thousands of years this proportion has been about 1 atom of C-14 for every 8.3 x atoms of carbon.

57. When an organism dies the C-14 decays slowly, so the proportion of C-14 is reduced over time
C-14 has a half-life of 5730 years, making it very useful for the measuring ages of objects that are a few thousand to several tens of thousands of years old.
To measure