Nuclear pharmacy

Basics
• All substances are made of atoms .
• These have electrons(e) around the outside (negativelycharged),
and a nucleus in the middle.
• The nucleus consists of protons (positively charged) and neutrons
(neutral).
• The atomic number of an atom is the number of protons in its nucleus.
• The atomic mass is the number of protons + neutrons in its nucleus.
• Isotopes of an atom have the same number of
protons, but a different number of neutrons.
• Example:
Consider a carbon atom:
It has 6 protons and 6 neutrons - we call it
"carbon-12" because it has an atomic mass of
12 (6 plus 6).
One useful isotope of carbon is "carbon-14",
which has 6 protons and 8 neutrons.
• Radioisotopes, Radionuclides:
unstable isotopes which are distinguishable by
radioactive transformation
• Radioactivity: the process in which an unstable
isotope undergoes changes until a stable state
is reached and in the transformation emits
energy in the form of radiation (alpha particles,
beta particles and gamma rays).
• Radiation refers to particles or waves coming
from the nucleus of the atom (radioisotope or
radionuclide) through which the atom
attempts to attain a more stable configuration.
 Radioactive decay
• Radioactive decay is the process in which an
unstable atomic nucleus spontaneously loses
energy by emitting ionizing particles and
radiation.

• This decay, or loss of energy, results in an atom

of one type, called the parent nuclide
transforming to an atom of a different type,
named the daughter nuclide.
• Half life (t1/2): the time taken for the activity of
a given amount of a radioactive substance to
decay to half of its initial value.
Type of Radiation Alpha particle Beta particle Gamma ray

Symbol

Charge +2 -1 0

Speed slow fast Very fast

Ionising ability high medium 0

Penetrating low medium high

power

Stopped by: paper aluminium lead

 introduction
Radiopharmacy = Nuclear Pharmacy

Defi: Nuclear pharmacy is a specialty area of

pharmacy practice dedicated to the
compounding and dispensing of radioactive
materials for use in nuclear medicine
procedures.”
• Radiopharmacy is a subspeciality of pharmacy deals with
receiving, preparation, quality control, storage and
dispensing of radiopharmaceuticals.
- It also deals with disposal of radioactive waste and
documentation of each operation.
- furthermore, radiopharmacy may be engaged in research,
designing and development of new radiopharmaceuticals.
• Radiopharmacy may also be called as hot laboratory
because of processing radioactive material- which
sometime referred as hot materials
• 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.
• Radiopharmaceuticals usually have no
pharmacologic effect, because in most cases
they are used in trace quantities.
• Differ from conventional drugs but they
should be sterile and pyrogen free.
• 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
 Discriminatory properties of
radiopharmaceutical
 Presence of radioactivity
due to presence of radionuclide (radioactive
atom) as an integral part of radiopharmaceutical,
it is associated with the emission of radiation.
Thus, requiring special precautions during
handling
 Scarcity of pharmacologic effect
it do not produce pharmacologic effect, because
its trace quantity is used
 Having short shelf life it also poses constrain
for QC check before administration to patients
 Usual route of administration most of
radiopharmaceuticals are prepared as sterile
and pyrogen-free i/v solutions to be
administered directly to patients. Other less
common routes are oral and inhalation, e.g.,
radioactive gases and aerosols
 Dose measurement in term of radioactivity unit
dose is measured in units of radioactivity rather then mg or ml.
1 MBq (27 microcuries) (M for méga)
1 GBq (27 millicuries) (G for giga)
37 GBq (1 curie)
1 TBq (27 curies) (T for tera )

• Conversion Equivalence
• 1 curie = 3.7 x 1010
disintegrations per second
• 1 becquerel = 
1 disintegration per second

In the International System of units (SI), the becquerel (Bq) is the unit of radioactivity.
One Bq is 1 disintegration per second (dps). One curie is 37 billion Bq. 
One Bq is defined as the activity of a quantity of radioactive material in which one 
nucleus decays per second. The Bq unit is therefore equivalent to an inverse
second,s−1.
 Half lives of radiopharmaceutical
the half lives of radiopharmaceuticals taken in
consideration are physical half life, biological half life and
effective half life.
- physical half life is the time necessary for the radioactive
atoms to decay to one half of their original number.
- biological half life is the time required for the body to
eliminate one half of the administered doses of any
radiopharmaceutical by the process of biologic
elimination
- effective half life is the time required for an administered
radiopharmaceutical dose to be reduced by one half due
to physical decay and biological elimination
 Practice regulation
the practice of radiopharmaceutical as well as the
premises for this practice requires NOC from Pakistan
atomic energy commission.
Basic requirements include licensure, facilities (space,
equipments), also radioisotope committee and
environmental control is required
 Ideal radiopharmaceutical
• Easy availability
• Effective Half-Life
• Particle Emission
• Decay by Electron Capture or Isomeric
Transition
 Production of radionuclides
1- Charged particle bombardment
Radionuclides may be produced by bombarding
target materials with charged particles in
particle accelarators such as cyclotrons.
- A cyclotron consists of :
Two flat hollow objects called dees.
The dees are part of an electrical circuit.
On the other side of the dees are large magnets
that (drive) steer the injected charged
particles (protons, neutrons, 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
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
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.
• Tc generator consist of column containing
99m

alumina on which Molybdenum 99 is absorbed in

form of ammonium molybdate
• Radioactive decay of 99 Mo produces 99mTc
which is eluted from the column
• This isotope is produced for brain , liver and in
thyroid scanning and is safer
• It has short half life and does not emit beta
radiations.
 Preparation of Radiopharmaceuticals

• 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.
 the synthesis of a radiolabelled compound
via a multi-step preparation process.
• The process of compounding
radiopharmaceuticals must be under the
supervision of recognized nuclear physician or
a radio pharmacist.
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.
 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.
 Labeling

The label on the outer package should include:

1. a statement that the product is radioactive or
the international symbol for radioactivity.
2.the name of the radiopharmaceutical
preparation;

3.the preparation is for diagnostic or for

therapeutic use;

4.the route of administration;

5.the total radioactivity present

6.the expiry date

7.the batch (lot) number

8.for solutions, the total volume;

9.any special storage requirements with respect to

temperature and light;

10.the name and concentration of any added

microbial preservative
Protective measures/radiation protection

• Adequate shielding must be used to protect

laboratory personnel from ionizing radiation.
• The radiation protection is safekeeping of
worker from the hazard of radiation to a level
as low as reasonably achievable (ALARA
principle). This can be achieved by preventing
spills and spread of contamination outside the
laboratory
• Another important aspect of radiation
protection is sensible use of time, distance
and shielding (TDS). The time spent in
radiation area, intensity of radioactivity,
distance from radiation source and shielding
(lead shielding for gamma rays and plastic,
glass or alumium for beta particulate emitting
radiopharmaceuticals) are the basic and
critical elements of radiation safety
• Other general roles for safety
- all members of department are responsible to
protect themselves and other persons as well
from radiation hazards
- know the rules, area designation and signs
set forth for the radioactive materials
- wear the protective dressing while working
with radioactive materials
• The fume-generating radioactive materials (e.g.,
radioiodine and radioxenon) must be handled in
the isolator fitted with fume hood
• Perform so that there is minimum waste
production and wash hands on completion of
procedure
• When needed, transport the radioactive
material in the trolley or in a tray lined with
disposable cloth, etc
 QC of radiopharmaceuticals
• The quality control of radiopharmceuticals is
the area of pharmacist.
• The radioactive materials administered to
patients are medicinal products and therefore
are expected to have the same degree of
quality and safety as any other
pharmaceutical.
 QC of radiopharmaceuticals
 Visual Inspection of Product
• Visual inspection of the compounded
radiopharmaceutical shall be conducted to
ensure the absence of foreign matter and also to
establish product identity by confirming that
(1) a liquid product is a solution, a colloid, or a
suspension.
(2) a solid product has defined properties that
identify it.
 Microbiological Control (sterility test) and Bacterial Endotoxin
Testing
 The QC tests are performed for sterility and pyrogenicity of the
produtcs.
 Limulus amebocyte lysate (LAL) test: Recently LAL test is
considered of merit for pyrogen testing of radiopharmaceutical
which gives an instant result.
 Assessment of Radioactivity
• The amount of radioactivity in each compounded
radiopharmaceutical should be verified and documented prior to
dispensing, using a proper standardized radionuclide (dose)
calibrator.
 Radionuclidic Purity
• Radionuclidic purity can be determined with
the use of a suitable counting device.
• The gamma-ray spectrum, should not be
significantly different from that of a
standardized solution of the radionuclide.
 Radiochemical purity
• Radiochemical purity is assessed by a variety of
analytical techniques such as:
– liquid chromatography
– paper chromatography
– thin-layer chromatography
– electrophoresis
the distribution of radioactivity on the chromatogram is
determined.
 Application of radiopharmaceuticals
The radiopharmaceuticals are applied for diagnostic ,
treatment and palliative care.
1.Therapeutic applications:
• The radiopharmaceutical for therapeutic use normally
contain a radionuclide that decays by emmiting a beta
particle
• They are radiolabelled molecules designed to deliver
therapeutic doses of ionizing radiation to specific diseased
sites.
• Exm:
• 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
• Strontium chloride Sr 89 for cancerous bone
tissue
 Application of radiopharmaceuticals

2. Diagnostic applications:
• In diagnostic applications, gamma emitting
radiopharmaceutical are used to probe(examen)
physiologic or pathophysiological functions of human body.
• 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.
• Exm:

• Radiopharmaceuticals used in tracer techniques for

measuring physiological parameters (e.g. 51

Cr-EDTA for measuring glomerular filtration rate).

• Radiopharmaceuticals for diagnostic imaging

(e.g.99m TC-methylene di phosphonate (MDP) used

in bone scanning).
• Other diagnostic radiopharmaceutical used
are technetium-99m, Iodine-123, indium-111,
thalium-201 and galium-67
3. Palliative applications
• The radiopharmaceutical used to improve the
quality of life of a patient but can not eradicate a
disease provide palliative care.
• Examples are strontium-89 and phosphorous-
32, which are used to relieve pain due to cancer
metastasis in bone at terminal cancer stage
patients
 Role of pharmacist
• Hospital pharmacist may assume the responsibility for
the ordering, receiving and storage of all isotopes use in
the hospital
• All packages coming to pharmacy must be stored in a
lead vault and date and time of receipt, purchase order
number, name of isotope and quantity received is
recorded
• The radiation safety officer or the radiopharmacist
(depending on the local policy of the hospital) monitors
the pharmacy vault and the surrounding area as part of
safety program
• All records of isotope materials received are to
be maintained in the pharmacy office and
made available to the radiation safety officer
and the atomic energy commission inspector
when necessary.
• The disposal of waste products will fall under
the guidance of radiopharmacist with
collaboration of the radiation safety officer
Responsibilities of radiopharmacist
• Ordering, receiving and keeping the record of all radioactive
materials and cold kits
• Implementation of good pharmaceutical and good
radiopharmaceutical practices
• Implementation of radiation protection and safety policy in
radiopharmacy lab, gamma counter room and injection area
• Performing QC tests
• Supporting and active participation in research projects
• Training to the technologist on the pharmaceutical aspects
of the nuclear medicine, radiation biology and protection
 Summary

• Nuclear pharmacy/radiopharmacy and radiopharmaceuticals

• Discriminatory properties of radiopharmaceuticals
• Production of radionuclide
• Preparation of radiopharmaceuticals/sterilization
• Radiation protection/Protective measures
• Waste disposal of radiopharmaceuticals
• labelling
• QC of radiopharmaceuticals
• Application of radiopharmaceuticals
• Role of pharmacist