Radiopharmaceuticals

1. 1
RADIOPHARMACEUTICALS

2. We will Cover the Following Points:
 What Are Radioisotopes?
 Radioactive Decay
 Radiation Units
 Radiopharmaceuticals
 Properties of an Ideal Diagnostic Radioisotope
 Radiopharmaceutical Categories & Production
 Radiopharmaceutical Quality Control
 Radiation Measurement
 Application of Radiopharmaceuticals
 Journey of a Radiopharmaceutical

3. • Radioactive Decay.
An unstable atomic nucleus spontaneously loses energy by emitting
ionizing particles and radiation.
Radioactive isotope Parent Nuclide Daughter Nuclide
When an unstable nucleus decays, it may give:
1) Alpha or helium Radiation.
2) Beta or Electron Radiation.
3) Gamma Radiation.

4. 1) ALPHA PARTICLE DECAY
• Alpha particles are made up of 2 protons and 2 neutrons.
• Are same as helium nucleus.
• When a nucleus emits alpha particle, its atomic number
decreases by 2 and its atomic mass decreases by 4.
• These particles are relatively slow and heavy.
• Low penetrating power.
• As they have large charge, alpha particles ionize other
atoms strongly.
• Alpha decay occurs in very heavy elements like Uranium
and Radium.

5. 2) Beta Particle Decay
• These particles are as same as electrons as they have
charge of minus 1.
• When a nucleus emits β particle the Atomic number
increases by 1 and Atomic mass is unchanged.
• They are fast and light.
• Have Medium Penetrating Power.
• Example of radioisotope emitting β, phosphorus-32.
• These particles ionize atoms that they pass, but not as
strongly as alpha particles do.

6. 3) GAMMA RAYS
• Gamma rays are Waves not Particles.
• They have no mass and no charge.
• Atomic mass and number unchanged.
• High Penetrating Power.
• Do not directly ionize other atoms.
• We don’t find pure gamma source, they are emitted along
alpha or beta particles.
• Useful gamma source technetium-99, used as tracer in
medicine.

9. HALF-LIFE
• The half life of radioisotope is the time for the radiation
level to decrease (decay) to one half of the original value.
• Naturally occurring tend to have longer half lives.
• Used in nuclear medicine have short half lives.
Radioisotope Half Life
14 C 5730 year
40 K 1.3 x 109year
226 Ra 1600 year
238U 4.5 x 109 year
59 Fe 46 days
57 Cr 28 days
131 I 8 days
99m Tc 6 hrs

10. Radiation Units
1. Curie (Ci)-measures activity as the number of atoms that
decay in one second.
2. rad (radiations absorbed dose)- Measures the radiation
absorbed by the tissues of the body.
3. rem (radiation equivalent mass)- Measures the biological
damage caused by different types of radiation.
4. Becquerel (Bq) - 1Bq = 1 Disintegration per sec (dps)
5. Sievert (Sv) = 100 rem
6. Gray (Gy) = 1 J/Kg Tissue

11. Radiopharmaceuticals
These are medical formulation containing radioisotopes.
• Composed of two parts: Radionuclide + Pharmaceutical.
• Nuclide - Any species of atom characterized by a specific
number of neutrons and protons within the atoms.

12. Properties of an Ideal Diagnostic Radioisotope:
• Type of Emission:
-Pure Gamma Emitter: (Alpha & Beta particles are
unimaginable & deliver High Radiation Dose)
• Energy of Gamma Rays:
-Ideal: 100-250 keV
• Photon Abundance:
-Should be high to minimize imaging time
• Easy available:
-Readily available, easily produced and inexpensive
• Target to Non Target Ratio
-Should be high which max efficiency and min the radiation

13. • Effective Half Life
-It should be short enough to minimize the radiation dose to
patients and long enough to perform the procedure.
• Patients Safety
- Should not exhibit toxicity to the patients.
• Preparation Quality Control
- No complicated equipment
- No time consuming steps

14. Radiopharmaceuticals can be divided into Four
Categories:
1. Radiopharmaceutical Preparation
2. Radionuclide Generator
3. Radiopharmaceutical precursor
4. Kit for Radiopharmaceutical Preparation.
Manufacture
-Radionuclide Production
1. Nuclear Fission
2. Charged particle bombardment
3. Neutron Bombardment
4. Radionuclide Generator System

15. • Example of Production of Technetium 99
• Uranium 235 is bombarded with neutrons which splits
into Molybdenum 99 and other particles.
• Molybdenum 99 undergoes β decay to produce
Technetium 99m

16. Production of Radiopharmaceutical Preparation.
1) Sterilization
For heat stable products- Autoclave.
For heat labile products- Using membrane filtration of the
radiopharmaceutical using 0.22 μm Millipore filters.
2) Addition of anti microbial preservative.
- The nature of the antimicrobial preservative, if present, is
stated on the label or, where applicable, that no antimicrobial
preservative is present.

18. Radiopharmaceutical Quality Control
i. Identity Test
The radionuclide is generally identified by its half-life or by
the nature and energy of its radiation or by both as stated in
the monograph.
ii. Radionuclides Purity
The gamma-ray spectrum, should not be significantly
different from that of a standardized solution of the
radionuclide.
iii. Radiochemical Purity
Assessed by a variety of analytical techniques such as liquid
chromatography, paper chromatography, thin-layer
chromatography and electrophoresis.

19. iv. Chemical Purity
Refers to the proportion of the preparation that is in the specified
chemical form regardless of the presence of radioactivity; it may be
determined by accepted methods of analysis.
v. pH
For radioactive solutions the pH may be measured using paper
pH indicator strips (Ideally should be in between 6.8 – 7.5)
vi. Sterility
a) Radiorespirometry
The sample of radiopharmaceutical is incubated in a culture
medium containing 14C glucose or 14C acetate at 37°C for 3-
24 h. If bacteria are present in the sample, they metabolize the
14C-glucose or 14C-acetate, which is measured in a liquid
scintillation counter. Radiorespirometry is a faster technique
for sterility testing of radiopharmaceuticals.

20. b. Colony culture
The sample of radiopharmaceutical is incubated in thioglycolate
medium (30-35°C) for aerobic and anaerobic bacteria or in
soybean casein medium (20-25°C) for fungi, molds. The test
medium is observed for 7-14 days. The presence or absence of
micro-organism in the sample is determined by bacterial growth
or lack of it in the culture.
vii. Bacterial Endotoxin/ Pyrogen Testing
- For Bacterial Endotoxin Test- LAL Test
- For Pyrogen Test – Rabbit Pyrogen Test

21. viii. Labeling

22. Storage
-Should be kept in well closed container
-Storage condition should be such that maximum
radiation dose rate to which persons maybe be exposed
is reduced to an accepted level.
-Radiopharmaceutical preparation intended for
parenteral use should be kept in glass vials, ampule or
syringe that is sufficiently transparent to permit the
visual inspection of the contents.

23. • Radiation Measurement
1. Geiger Muller Counter
- Detects beta and gamma radiation.
- Uses ions produced by radiation to create an electrical
current.
- It is a gaseous ionization detector and uses
the Townsend avalanche phenomenon to produce an
easily detectable electronic pulse from as little as a
single ionizing event due to a radiation particle.
- a gas ionization process where free electrons are
accelerated by an electric field, collide with gas
molecules, and consequently free additional electrons.

26. 2. Scintillation Counter
- An instrument for detecting and measuring ionizing radiation by
using the excitation effect of incident radiation on a scintillating
material, and detecting the resultant light pulses.

27. • Applications of Radiopharmaceuticals.
1. Treatment of diseases (Therapeutic Radio Pharmaceuticals):
- They are radio labeled molecules designed to therapeutic doses of
ionizing radiation to specific diseased sites.
Examples:
 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 P32 for cancerous bone tissue and
other types of cancers
 Strontium chloride Sr 89 for cancerous bone tissue
 Erbium 169 for relieving arthritis pain in synovial joints

28. 2. As an aid in the diagnosis of disease
(Diagnostic Radiopharmaceuticals)
- The Radiopharmaceutical accumulated in an organ of
interest emit gamma radiation which are used for imaging
of the organs with the help of an external imaging device
called gamma camera.
- Radiopharmaceutical used in tracer techniques for
measuring physiological parameters (eg. 51 Cr EDTA for
measuring Glomerular filtration rate).
- Radiopharmaceuticals for diagnostic imaging (eg. 99m
TC-methylene diphosphonate(MDP)used in bone
scanning).

29. - PET (Positron Emission Tomography) and
- SPECT (Single Photon Emission Tomography) are
imaging technologies that enable physicians to
diagnose different types of cancer, cardiovascular
diseases, neurological disorders and other diseases in
their early stages.
PET SPECT
Involves Positron Involves Gamma Rays
More Sensitive Optimum Sensitivity
Higher Resolution Lower Resolution
Detection by PET Scanner Detection by Gamma Camera
Expensive Scanner Cheaper than PET
Limited Half life of
Radiopharmaceuticals
Longer Half life of
Radiopharmaceuticals

30. Journey of
A Radiopharmceutical