Download Instruments for Radiation Detection and Measurement

QUALITY CONTROL OF
RADIOPHARMACEUTICALS
Lab # 5
Quality Control of
Radiopharmaceuticals


Radiopharmaceuticals they undergo strict quality
control measures
Involves several specific tests and measurements that
ensure
 Purity
 Potency
 Product
identity
 Biologic safety
 Efficacy
A- Physicochemical Tests


Tests that are essential for the
determination of the purity and
integrity of a radiopharmaceutical.
Some of these tests are unique for
radiopharmaceuticals because they
contain radionuclides.
1- Physical Characteristics




One should be familiar with the color and state of a
radiopharmaceutical
A true solution should not contain any particulate matter
Any deviation from the original color and clarity should be
viewed with concern because it may reflect changes in the
radiopharmaceutical that would alter its biologic behavior
Colloidal or aggregate preparations should have a proper size
range of particles for a given purpose
2- pH and Ionic Strength



All radiopharmaceuticals should have an
appropriate hydrogen ion concentration
or pH for their stability and integrity
Ideal pH of a radiopharmaceutical
should be 7.4
pH can vary between 2 and 9 because
of the high buffer capacity of the blood
2- pH and Ionic Strength




Measured by a pH meter
Radiopharmaceuticals must also have proper
 Ionic strength
 Isotonicity
 Osmolality
in order to be suitable for human administration
How to achieve Correct ionic strength?
By adding a proper
 Acid
 Alkali
 Electrolyte
3- Radionuclidic Purity

Defined as
 The
fraction of the total radioactivity in the form of the
desired radionuclide present in a radiopharmaceutical
 A compound has absolute radionuclidic purity if it
contains no radionuclide other than the one of interest.
 The radionuclidic purity is an essential parameter in the
quality control of radiopharmaceuticals

Impurities arise from
1.
2.
Extraneous nuclear reactions due to isotopic impurities
in the target material
Fission of heavy elements in the reactor
3- Radionuclidic Purity



The undesirable radionuclides may belong to the
same element as the desired radionuclide or to a
different element
Impurities can be removed by appropriate chemical
methods
Radionuclidic purity is determined by measuring the
half-lives and characteristic radiations emitted by
individual radionuclides
4- Radiochemical Purity

Defined as

The fraction of the total radioactivity in the desired chemical form in the
radiopharmaceutical

Radiochemical purity is important in radiopharmacy since it is the
radiochemical form which determines the biodistribution of the
radiopharmaceutical. Radiochemical impurities will have different patterns
of biodistribution which may obscure the diagnostic image obtained and
render the investgation meaningless.
4- Radiochemical Purity

The presence of radiochemical impurities in a
radiopharmaceutical results in poor-quality images
due to the high background from the surrounding
tissues and the blood, and gives unnecessary
radiation dose to the patient
4- Radiochemical Purity

Radiochemical impurities arise from
1.
Decomposition due to the action of
solvent
2.
Change in temperature or pH, light
3.
Presence of oxidizing or reducing
agents
4- Radiochemical Purity

Decomposition of labeled compounds by
radiolysis depends on
1.
2.
3.
The specific activity of the radioactive material
The type and energy of the emitted radiation
The half-life of the radionuclide
4- Radiochemical Purity
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Absorption of radiations by labeled molecules
results in the formation of free radicals with
unpaired electrons
Which in turn leads to further decomposition of
other molecules.
A secondary process due to radiolysis produces
H2O2 or HO2 : from decomposition of water
(solvent)
Which reacts with and ultimately decomposes
labeled molecules.
4- Radiochemical Purity
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

1.
2.
The stability of a compound is time-dependent on
exposure to light, change in temperature, and radiolysis
The longer a compound is exposed to these conditions,
the more it will tend to break down
How to lessen the degradation of the material?
Substances such as sodium ascorbate, ascorbic acid, and
sodium sulfite are often added to maintain the stability
of radiopharmaceuticals
Some radiopharmaceuticals are stored in the dark
under refrigeration
4- Radiochemical Purity

Analytical methods used to detect and determine the
radiochemical impurities in a given radiopharmaceutical:
1.
2.
3.
4.
5.
6.
7.
8.
Precipitation
Paper and Instant Thin-Layer Chromatography
Gel Chromatography
Paper or Polyacrylamide Gel Electrophoresis
Ion Exchange
Solvent Extraction
High-Performance Liquid Chromatography
Distillation
5- Chemical Purity
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

The fraction of the material in the desired chemical
form whether or not all of it is in the labeled form
Aluminum is a chemical impurity in the 99mTc-eluate
The presence of a slight amount of globulins in the
preparation of albumin is indicative of impurities
5- Chemical Purity

The presence of chemical impurities before
radiolabeling may result in
1.
2.
Undesirable labeled molecules that may or may not
interfere with the diagnostic test
Undue chemical impurities may also cause a toxic
effect
5- Chemical Purity

Purification of radiopharmaceuticals from
Chemical impurities is often carried out by
methods of chemical separation such as
1.
2.
3.
4.
Precipitation
Solvent extraction
Ion exchange
Distillation
6- Radioassay
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

The amount of radioactivity of a radiopharmaceutical
before dispensing as well as that of each individual
dosage before administration to patients must be
determined
These activity determinations are carried out by using a
dose calibrator
The performance of the dose calibrator must be
checked by carrying out several quality control tests.
6- Radioassay
Dose Calibrator Quality Control

According to the NRC regulations the following quality
control tests must be performed at the frequencies
indicated:
1. constancy (daily)
2. accuracy (at installation, annually, and after repairs)
3. linearity (at installation, quarterly, and after repairs)
4. geometry (at installation and after repairs)
6- Radioassay
Dose Calibrator Quality Control
1.
constancy (daily)

The constancy test indicates the reproducibility of
measurements by a dose calibrator
2. accuracy (at installation, annually, and after repairs)
 The accuracy of a dose calibrator is determined by
measuring the activities of at least two long-lived
reference sources and comparing the measured activity
with the stated activity
 The measured activity must agree with the stated
activity within ±10%.
6- Radioassay
Dose Calibrator Quality Control
3. linearity (at installation, quarterly, and after repairs)
 The linearity test indicates the dose calibrator’s ability
to measure the activity accurately over a wide range
of values
4. geometry (at installation and after repairs)
 Variations in sample volumes or geometric
configurations of the container
 Correction factors must be established for changes in
volume or container configuration
B- Biological Tests

Carried out essentially to examine
1. The sterility
2. Apyrogenicity
3. Toxicity
of radiopharmaceuticals before
human administration
Biological Tests
1- Sterility


Sterility indicates the absence of
any viable bacteria or
microorganisms in a
radiopharmaceutical preparation
Methods of Sterilization
1.
2.
Autoclaving
Membrane Filtration
Biological Tests
2- Apyrogenicity
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All radiopharmaceuticals for human administration are required to be pyrogen
free
Pyrogens are either polysaccharides or proteins produced by the metabolism of
microorganisms
They are 0.05 to 1 mm in size, soluble and heat stable
Following administration pyrogens produce symptoms of
 fever, chills, malaise, leukopenia, pain in joints, flushing, sweating, headache,
and dilation of the pupils
Pyrogenicity Testing
1.
USP Rabbit Test
2.
LAL (limulus amebocyte lysate)Test

The principle of the test is based on the
formation of an opaque gel by pyrogens upon
incubating the sample with the LAL at 37C

The reaction takes place within 15 to 60 min
after mixing and depends on the concentration
of pyrogens
C- Record Keeping

Record keeping is mandatory for legal reasons as
well as for tracing any faulty preparation