Radio-Pharmacy Techniques

& Applications
Radio-Pharmacy
• Radio pharmacy is also called as, ‘Nuclear Pharmacy.’ It is a special
area of pharmacy practice dedicated to the compounding and
dispensing of radioactive materials for use in nuclear medicine
procedures
Radiopharmaceuticals:
• Radiopharmaceutical is composed of two words Radio means
‘radiations’ and Pharmaceuticals means ‘dosage form.’
Radiopharmaceuticals is defined as; these are dosage forms which
incorporate radio nuclide (radio isotopes) and hence they are
radioactive.
Isotopes:
• Isotopes can be defined as, “the atoms of an element having same
atomic no. but different mass no. is called as isotopes.” All substances
are made up of atoms. Atoms have electrons revolving around them
in the different energy levels. The nucleus consist of protons and
neutrons. The no. of protons present in the nucleus of an atom is
called as Atomic no. it is denoted by Z. The no. of protons &
neutrons present in the nucleus of an atom is called as Mass no. it is
denoted by A.
Radiations:
• Radiation refers to particles or waves coming from the nucleus of the
atom (radioisotopes or radionuclide) through which the atom
attempts to attain a more stable configuration.
Radioactivity:
• It is a process in which an unstable isotopes undergoes changes until
a stable state is reached and in the transformation emits energy in the
form of radiation.
Radionuclides:
• Radioisotopes of radionuclides are unstable isotopes which are
distinguishable by radioactive transformation
Radioactive decay
• It is a process in which an unstable atomic nucleus spontaneously loses
energy by emitting ionizing particles and radiations. 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: The time taken for the activity of a given amount of a
radioactive substance to decay to half of its original value. It is represented
by t1/2
Total activity: It is the number of decay an object undergoes per
second. It is represented with A.
Radionuclide purity: It is the percentage of the total radioactivity that
is present in the form of the stated radionuclide
Radiations
• Radiation refers to particles or waves coming from the nucleus of the
atom (radioisotopes or radionuclide) through which the atom
attempts to attain a more stable configuration. When an unstable
nucleus decays, it may give out;
Types of radiations
• 1. Particulate radiations
α – particles
β – particles
2. Electromagnetic radiations

γ – particles
i. α – particles:
• Alpha particles are made up of 2 protons and 2 neutrons. They are written
as 2He4 or 2α 4 . It means when a nucleus emits an alpha particle its mass
no. decreases by 4 and atomic no. will decreases by 2.
• Alpha decay occurs in heavy nucleuses like uranium etc. Properties: The
properties of α – particles are as fallows;
They are positively charged particles.
They are slow & relatively heavy particles.
They have short range.

They have low penetrating power.

They are not used in pharmaceutical preparations
β – particles:
• Beta particles have a charge of -1. They have same mass as electrons that is why they can
be written as −1𝛽 0 or −1𝑒 0 . That means when a nucleus emits a beta particle the mass
no. is unchanged and the atomic no. either decreases or increases by 1

• Properties:
• The properties of β – particles are as fallows;
• They have same mass as electron.
• They are fast and light.
• They may be negatively charged (electron) and may be positively charged (positrons).
• Its range is a few meters in air or about 10mm in body.
• Beta particles have medium penetrating power, they can be stopped by simple aluminum
sheet.
• These particles ionized atoms that they pass but not strongly as alpha particles do.
γ – particles
• Gamma rays are waves they have no charge and mass. The emission of Gamma
particle has no changing on mass no. and atomic no. We don’t fine pure gamma
source. Gamma rays are emitted alongside alpha and beta particles.

• Properties: The properties of γ – particles are as fallows;

• They has no mass. They have no charge.
• They travel with a speed of light.
• They are highly penetrating. It takes thick sheets of metals like lead to reduce
them.
• They are high energy rays can pass through several feet of solid matter.
• These rays don’t directly ionize other atoms. Although may cause other atoms to
emit other particles which will then cause ionization
Radioactivity
• It is a process in which an unstable isotopes undergoes changes until
a stable state is reached and in the transformation emits energy in the
form of radiation.
Types of Radioactivity
• Radioactivity is principally of two types;
• 1. Natural radioactivity
• 2. Artificial radioactivity
1. Natural radioactivity:
• Atomic nuclei having atomic no. greater than 82 naturally emits
radiations. Nuclear reactions or emissions occurs simultaneously. This
is called as natural radioactivity
2. Artificial radioactivity:
• The property of radioactivity produced by particle bombardment of
electromagnetic radiations.
• i. Charged particle reactions: The charged particles are bombarded
on the nuclei. For example; α – particles, protons etc.
• ii. Photon induced reactions: The source of electromagnetic energy
may be gamma emitting radionuclide or high voltage x-ray generator.
• iii. Neutron induced reactions: It is the most widely used method for
radioactivity. It includes the bombardment of a nonradioactive target
nucleus with a source of thermal neutrons
Radionuclides
• Radioisotopes of radionuclides are unstable isotopes which are
distinguishable by radioactive transformation.
Production of radionuclides
• Most of the radionuclides used in medicine and pharmacy are
produced by artificially. The various production method of
radionuclides are as fallows;
1. Charged particles bombardment:
• Radionuclides may be produced by bombarding target materials with
charged particles in particles in particle accelerators such as
cyclotrons. A cyclotron consist 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 (electrons, protons, deuterons or alpha particles) in a
circular path. The charged particles follows a circular path until the
particles has sufficient energy that is passes out of the field and
interact with target nucleus
2. Neutron bombardment:
• The majority of radiopharmaceuticals are produced by neutron
activation reactions by placing a suitable target material in a nuclear
reactor where it is bombarded by neutrons. By means of neutron
activation & transmutation reactions, reactors produce radionuclides
having a high neutron to proton ratio that typically decay by emission
of a negatron.

• Example: The radioactive phosphorus can be prepared from stable

phosphorous 31P by neutron capture.
3. Fission by products:
• Fission is a radioactive process in which a relatively heavy nucleus is
divided into two new nuclei of nearly equal size with the
simultaneous emission of two or three neutrons. Fission may be
spontaneous, but normally the reactions is induced by bombardment
of the parent nucleus with neutron
4. Radionuclide generator system:
• 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.
99Mo/ 99mTc Generator:
• Technetium 99m is the most commonly used metal atom in radiopharmaceuticals; probably 75%
of all radiopharmaceuticals include 99mTc as the radionuclide. Technetium 99m is derived from
the decay of parent nuclei 99Mo as molybdate (99MoO4 -1 ). Since, 99Mo decays to daughter
nuclei 99mTc, it is chemically separated and used to make various 99mTc radiopharmaceuticals.
This separation process occurs in 99Mo/ 99mTc radionuclide generator system. Alumina is used as
an adsorbent material for 99Mo. The 99mTc is eluted in the form of Sodium pertecnetate (
99mTcO4 -1 ) in normal saline solution, in +7 oxidation state. It is not reactive as such therefore
the oxidation state is reduced to lower value.

• Features of Technetium:
• It has desirable physical properties of imaging purposes.
• It has a half-life of 6 hours.
• It has a 140 KeV gamma photon that is emitted with very high abundance.
• It has a versatile chemistry that allows it to be chelated with a variety of compounds.
Preparation of Radiopharmaceuticals
• The preparation of radiopharmaceutical consist of following steps
• 1. Sterilization
• 2. Addition of antimicrobial preservative
• 3. Compounding:
1. Sterilization:
• Radiopharmaceuticals intended for parenteral administration therefore
they must be sterilized by a proper and suitable method of sterilization.
• Sterilization is performed by either of the two ways;
1. The formulation is terminally sterilized. The Autoclaving method is
recommended for heat stable products. The final product is placed in the
autoclave and is sterilized at specified temperature.
2. The Filtration method is recommended for heat labile products. In
this method, the formulation is passed through Millipore filters and filtration
is done by applying pressure. Thus, the solid impurities and even microbes
are filtered out of the preparation. Finally the filtered formulation is then
transferred into the vial.
2. Addition of antimicrobial preservative:
• Radiopharmaceutical injections are commonly supplied in multidose
containers.
• The requirement of the general monograph for parenteral
preparations that such injections should contain a suitable
antimicrobial preservative in a suitable concentration does not
necessary apply to radiopharmaceutical preparations.
• A reason for the exemption is that many common antimicrobial
preservatives (for example; benzyl alcohol) are gradually decomposed
by the effect of radiation in aqueous solution.
3. Compounding:
• The process of compounding radiopharmaceuticals must be carried
out under the supervision of recognized nuclear physician or a
radiopharmacist. The compounding process of a radiopharmaceutical
can be as simple as; adding a radioactive liquid to a commercial
available Kit.
• It can be as complex as;
• The creation of a multi-component reagent Kit.
• The synthesis of radiolabelled compound via a multi-step preparation
process.
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
KIT:
• It is single sterile & pyrogen free, freeze dried rubber cap vial which
contain all necessary non-radioactive ingredients (complexing agent,
reducing agent, stabilizer, or dispersing agent) to prepare a specific
radiopharmaceuticals, and such vials are commonly referred to as
‘Kits.’
• These are formulated near the patients as the radioactive drug keeps
on decaying due to half-life.
Preparation of KITs:
• The preparation of kit is as fallows;
• Take a suitable size vials.
• Now clean and antiseptize the top with cotton.
• Now calculate the radioactivity of radio nuclei in radioactivity units.
• Sometimes manufacturer specifies that how to add the radioisotopes and
how much is to be added. Its minimum and maximum quantity is
mentioned on the Kit.
• Now add the radio nuclei to the vial with the help of a sterile syringe.
• Shake it well to mix the components with water.
• The preparation is ready for administration.
Advantages of KITs:
• It has following benefits;
• There is no exposure of radiations during the preparation of kit.
• It minimizes the exposure during handling or preparing a
radiopharmaceuticals.
• It also minimizes the administration of any microorganism to the
radiopharmaceuticals.
• While dealing with a radiopharmaceuticals one must take care about;

• 1. The half-life of the radioisotopes. Half-life is defined as time taken for the activity to fall to half of its
original value. Each nuclei has its own specific half-life. It is from fractions to seconds to years, but we use
isotopes of few seconds to few minutes, or days to months.
• Isotopes with half-life of few minutes are used for diagnosis.
• Isotopes with half-life of days to months are used for the treatment or palliative care. Half-life of a
radio nuclei is also important for the preparation of dosage form.
• 2. We should notice that which type of radiations it is emitting, either it is emitting alpha, beta or gamma
radiations.
• 3. Dose calculation is specifically made in units of radioactivity.
• Curie: It was named on the name of the scientist Merie Curie. It is defined as 3.7 x 1010 atoms disintegrate
per second. It is converted into smaller unit Milicurie (3.7 x 107 ) and Microcurie (3.7 x 104 ).
• Becquerel: It was named on the scientist Hennery Becquerel. It is defined as one Becquerel is equal to 1
disintegration per second.
Labelling:
• The label on the outer package should
include;
• A statement that a product is radioactive or the
international symbol of radioactivity.
• The name of the radiopharmaceutical
preparation.
• The preparation is for a diagnostic or for
therapeutic use. The route of administration
• The total radioactivity content
• The expiry date
• The batch (lot) number
• For solution the total volume
• Any special storage requirements with respect to
temperature to light.
• The name of concentration of any added
microbial preservative.
Discriminatory features of Radiopharmaceuticals
• Radiopharmaceuticals differs from normal dosage forms, the discriminatory properties
are discussed below;
• In radiopharmaceuticals there is presence of radioactivity.
• Radiopharmaceuticals, either have very little pharmacological effect or they lack of
pharmacological effect.
• They have short half-lives.
• They are usually administered through parenteral route, but with exception of oral
(iodine capsule) and inhalation route (radioactive gases) is also used.
• The dose calculation is in radioactive units that is; Curie (Ci) and Becquerel (Bq).
• For the practice regulation radiopharmaceuticals, one needs license from atomic energy
commission.
• It has the description of the quantity of radioactive element used.
• In case of radiopharmaceuticals, always minimum quantity is prescribed
Properties of an ideal diagnostic Radioisotope
• An ideal diagnostic isotopes must have following properties;
• Types of emission:
• Energy of gamma rays:
• Photon abundance.
• Target to non-target ratio
• Effective half-life:
• Preparation & quality control
• Types of emission: They must be pure gamma radiation emitter. As alpha and beta particles are unimagable & deliver high
radiation dose.
• Energy of gamma rays: The energy must be within range;
The ideal energy of photon must be 100 – 250 KeV. For example; 99mTc, 127I etc.
Suboptimal range is greater than 100 and must be less than 250 KeV. For example; 201Tl has greater than 100 while 131I
has less than 250.

• Photon abundance: The photons must be produced in excess to minimize the imaging time.

• Easy availability: The radionuclide must be easily available, easy to produce and it must be inexpensive. For example; 99mTc.

• Target to non-target ratio: The target to non-target ratio must be high.

It minimizes the radiation dose to the patient.
It also maximizes the efficacy of diagnosis.

• Effective half-life: It should be short enough to minimize the radiation dose to patient and long enough to perform the procedure.
Ideally, 1.5 times the duration of diagnostic procedures. Example: for a bone scan which is a 4 hour procedure 99mTc phosphate
compound with an effective half-life of 6 hours are the ideal radiopharmaceuticals.

• Preparation & quality control: The preparation of radiopharmaceutical must be simple with very little manipulation. The steps
involve in its preparation shouldn’t be time consuming and no complicated equipment should be required for formulation
Applications of Radiopharmaceuticals
• The applications of radiopharmaceuticals are very limited. They are
used in either of the three ways;
• 1. Therapeutic applications
• 2. Diagnostic applications
• 3. Palliative applications
1. Therapeutic applications:
• They are radiolabelled molecules designed to deliver therapeutic
doses of ionizing radiation to specific diseased sites. The radiations
emitted form therapeutic radiopharmaceuticals cause damage
selectively to neoplastic cells within the body. The
radiopharmaceutical for therapeutic use normally contain a
radionuclide that decays by emitting a β – particles. The energy of β –
particle should ideally be within the range of 0.5 – 1.0 MeV to prevent
widespread dissemination of radiation from the target. The half-life is
normally of the order of several days in order to provide reasonable
time for action.
Example:
• Chromic phosphate 32P for lung, ovarian, uterine, and prostate
cancers.
• Sodium iodide 131I is used from thyroid gland cancer.
• Samarium 153Sm is used for cancerous bone tissue.
• Sodium phosphate 32P for cancerous bone tissue and other types of
cancers.
• Strontium chloride 89Sr for cancerous bone tissue
2. Diagnostic applications:
• Radiopharmaceuticals are used as an aid in the diagnosis of diseases.
The radiopharmaceutical accumulated in an organ of interest and
emit gamma radiations which are used for imaging of the organs with
the help of an external imaging device called gamma camera.
• Radiopharmaceuticals used in tracer techniques for measuring
physiological parameters. For example; 51Cr-EDTA for measuring
glomerular filtration rate.
• Radiopharmaceuticals are used for diagnostic imaging. For example;
99mTc-methylene diphosphate (MDP) used in bone scanning
3. Palliative applications:
• The radiopharmaceuticals used to improve the quality of life of a
patient but cannot eradicate a disease provide palliative care.
• Example: Strontium-89 and phosphorous-32 are the examples that
are used to relieve the pains due to cancer metastasis in bone at
terminal cancer stage patients