Radiopharmaceuticals:

• As the name suggests, they are pharmaceutical formulations consisting of radioactive

substances (radioisotopes and molecules labelled with radioisotopes), which are
intended for use either in diagnosis or therapy
WHAT ARE RADIOACTIVE SUBSTANCES????
✓Radioactive substances have a property of emitting rays or particles. Forty
radioactive elements are known as Uranium series, Thorium series and Actinium
series.

✓The elements are known as radioactive because they are unstable and undergo
decomposition along with emission of radiations or rays.

✓The radiations or rays which are emitted are following:

❑ Alpha rays
❑ Beta rays
❑ Gamma rays
✓ Any nucleotide which is not radioactive in nature is regarded as stable. To be stable, a
nuclide may possess appropriate energy.

✓ Those nuclides which undergo spontaneous nuclear change so as to attain stability by

emitting radiations are called as radionuclides or radioisotopes.
Radioactivity:
It is a natural and spontaneous process by which the unstable atom of one element emits or
radiates excess energy in the form of particles or waves.
The emitted particles or waves are called Ionizing radiations.
Most common form of radiations are
• α rays
• β rays
• Γ rays
❖They have two positive charge.
❖Alpha particle radiation consists of two neutrons and two protons, as they are charged they are
affected by both electric and magnetic fields.
❖Heavy metals have capacity to emit such type of rays.
❖The capacity of the alpha particle to penetrate materials is not very great, it usually penetrates
no more than a few centimetres in air and is absorbed by a relatively small thickness of paper
or human skin.
❖It has highest ionizing power.
❖These rays or particles have low penetrating power bcs of large and heavy nature.
❖Because of low penetrating power of alpha particles, elements which emit alpha rays do not
find use in biological applications because they cannot penetrate tissue.
❖88Ra 226 ---------------------------→ 86 Rn 222 + He 4
Radium
2
Radon
• These are heaviest particles.
• Symbolised as 2He4.
• They get deflected in electric and magnetic field.
• The produce fluorescence and phosphorescence in Zinc sulphide.
• Their energy is about 6 meV.

❖Beta-particle radiation consists of fast moving electrons.

❖They are affected by electric and magnetic fields.
• These have 2 types:
❖Electrically positively charged particles which are called ‘positrons’
❖Electrically negatively charged particles which are called ‘Negatrons’
❖Beta particles can penetrate up to 1 m of air. They are stopped by a few
millimetres of aluminium.
❖ They have greater penetrating power than that of alpha rays.
❖ Beta particles have negligible mass.
❖ These particles are usually accompanied by gamma radiation. Beta particles have less ionizing power than
alpha particles.
❖ Their ionising capacity is much less than that of alpha radiation.
❖ Beta particles are 8000 times smaller than alpha particles.
❖ Energy ranges from 2 to 3 meV.
• 6C
14 --→ 7N14 + β-1 30Zn
65 --→ 29Cu65 + β+1

Gamma rays: (γ)

❖ Gamma radiation does not consist of charged particles, it is a form of very short wavelength electromagnetic
energy.
❖ They have no mass or charge.
❖ These have been more penetrating than alpha and beta rays.
❖ Gamma radiation is very difficult to stop, it takes up to 30mm of lead.
❖ They are having the same character as that of very short electromagnetic waves called X-rays.
❖ Gamma rays are produced during disintegration of radioactive substances along with beta radiation
❖ They are uncharged and have poor ionizing power.
❖ Can produce nuclear reaction.
Isotope:
• Atoms having same atomic number but different mass numbers are called isotopes. ( nuclides)
• Same number of protons but diff number of neutrons.
• They are chemically same but different physical properties.
1 2 3
1H 1H 1H
Hydrogen Deuterium Tritium
Types of Isotope:
1. Stable isotope: stable in nature and don’t emit any kind of radiations e.g. 13C, 35Cl , 1H and 2H.
2. Radioactive Isotopes:
• These are naturally or artificially created isotopes of element having an unstable nucleus that
decays alpha, beta and gamma rays until stability is reached.
• The original nuclide is called parent and product is called as daughter nuclide.

b b-4
aX a-2X + alpha rays
Parent Daughter nuclei
Radioactive isotopes are also 2 types:
❖Naturally occurring: U235, Ra226
❖Artificial radionuclide: Al27 + He4 P30 + n1
13 2 15 o

Half life:
• It is defined as the time required for a radioactive isotope to decay to one half of it’s original
value at any given point of time.
• Suppose we have 64 micro curies of radioactivity in a given sample of ferric citrate solution
After 1st t1/2 life period i.e. after 45 days: 32 mCi and then after 2nd half life its 16 micro
curies, after third half life its 8 micro curies and like wise.
t1/2 = 0.693/λ
Where λ= Disintegration constant.
Units of radioactivity
1. Curie ( c ) : Defined as quantity of any radioactive substance which undergoes the same
number of disintegrations in unit time as of 1 g of radium and is equal to
3.7 x1010 disintegrations per second.

2. Roentgen: it is the unit of exposure 1R= 2.58 x 10-4 coulomb kg-1

3. RAD ( Radiation absorbed dose) : it is the unit of absorbed dose. Pharmaceutical dosage
forms are described in RAD units.

4. REM (Roentgen equivalent man): It is unit of dose equivalent.

5. RBE (Relative biological effectiveness): shows effect of radiation, alpha, beta and
gamma on the biological system.

6. Becquerel (Bq): In the International System (SI), the unit of radioactivity is one nuclear
transmutation per second
Handling and storage of radiopharmaceuticals:
❖Great care needs to be taken in handling and storage of radioactive materials for protecting
people and personnel who handle it, from the harmful radiation they emit.
❖Certain precautions have to be taken while working with detectors, tracer equipment, radio
assay manufacturing or handling of radioactive materials.
❖In order to have protection from hazards of radiation, radioactive materials must be stored in
an area not frequently visited by people.
❖Shielding may be required.
❖Thick glass or Perspex containers provide sufficient shielding.
❖To protect from gamma rays (high penetration power), lead shielding has to be used.
❖The storage area must be regularly checked for radioactivity.
• RADIOACTIVE LIQUIDS.
❖Working area should not get contaminated with radioactive material.

❖If radioactive liquid is to be handled, it must be carried in trays with absorbent tissue paper,
so that any spillage will get absorbed by the paper.
❖Rubber gloves have to be used when working with radioactive liquids.
❖Pipettes operated by mouth should never be used.

❖Waste of radioactive material has to be stored till its activity becomes low and then only it
should be disposed.
PRECAUTIONS :
While handling and storage of radioactive substances:
1. One should not touch the radioactive emitter with hand but it should be handled by means
of forceps.
2. Smoking, eating and drinking activities should not be handled in laboratory where
radioactive material is handled.
3. Sufficient protective clothing and shielding have to be used while handling of materials.
4. Radioactive materials have to be stored in suitable labelled containers, covered (shielded by
lead bricks) and preferably in a remote corner.
5. Areas where radioactive materials are stored should be monitored and tested for
radioactivity regularly.
6. Disposal of radioactive materials should be carried out with great care.
• Strict requirements are prescribed by the department of Atomic energy (DAE) for the
establishment of a radioactive facility in the hospital or pharmacy.
These include specifications for premises, storage space, working area,
disposal protocol, training of personnel, periodic check on contamination or leakage.
Sodium iodide ( I131):
Synonym: radioactive Iodide
Preparation: It is Prepared in nuclear reactor by neutron irradiation of natural
Tellurium target.

β_
Te130 + n
0
1
Te131 + Ƴ I131
Properties:
It forms a colourless solution.
Have half life of 8.4 days and emit beta and gamma radiations.
Its solution having pH of 7 to 10.
• Give uses of Sodium iodide I-131
❖Used as a diagnostic aid for studying the functioning of the thyroid gland.
❖Used in scanning the thyroid for determining the size, position and possible tumour
location.
❖Used in the treatment of severe cardiac disease (Sodium iodide I-131), which reduces
work load on heart.
❖Radioactive iodine in thyroid carcinoma (cancer): The isotope is used most frequently
after the surgical removal of cancer to treat any residual tumour tissues.
Applications of Radioisotopes:
• They find use in medicine in 4 different ways:
1. Radioisotopes in Therapy (Emitted radiations used to destroy cells in condition
like cancer
2. Radioisotopes in Diagnosis (Radioactive tracers)
3. Research (Biological and medicinal studies by use of radioactive isotopes as tracers)
4. Sterilization (For sterilization of pharmaceuticals and surgical instruments)
1. In therapeutics:

✓ Radioactivity can be used in medicine and pharmacy in different areas, the first being
radiology, in which an external source of radioactivity passes through a patient and radiation
is absorbed by more dense tissues and not by less dense tissues and an image is ultimately
formed.
✓ The second is radiation therapy, which treats for tumors using an external source of radiation
to try and ablate ( remove surgically) a tumor.
✓ This requires lots of radiation in very high doses.
✓ Nuclear medicine uses an internal source of radiation to be detected externally.
✓ Radiopharmaceuticals can be used to destroy malfunctioning cells. This method of therapy is
called radiotherapy.
✓ It can be used for both benign and malignant cancers. (Benign tumors tend to grow slowly and do
not spread. Malignant tumors can grow rapidly)
• Examples:
❖Gold (198 Au) is used in treatment of malignant tumours. It is given in the form of colloidal
gold suspension.
❖Gold (198 Au) also used in treatment of carcinoma of uterus and urinary bladder.
❖Cobalt labelled cyanocobalamine (vitamin B12) is used in diagnosis of pernicious
anaemia.
❖Sodium iodide preparation finds use in treatment of thyroid disorders.
❖Calcium is used to study bone structure and in carcinoma of bone.
❖Strontium 90 is used in diagnosis of superficial carcinomas.
2. In diagnosis:
✓ Radiopharmaceuticals are developed based on the ADME (absorption, distribution,
metabolism, excretion) properties of the body.
✓ By administering a radiopharmaceutical to a patient, images of the targeted site can be
produced by a gamma camera.
✓ The images can then be analyzed by the nuclear medicine doctor to detect any medical
problems.
✓ Radiopharmaceuticals are most widely used to detect various forms of cancer.
✓ Depending on the site for diagnosis, there is a specified route of administration.
❖ Examples of Radioactive tracers find use in medicine for diagnostic purposes.
1. Labelled cyanocobalamine finds use for measuring the glomerular filtration rate.
2. Ferric citrate injection finds use for the diagnosis of haematological disorders.
3. Colloidal gold injection is used diagnostically to study blood circulation in liver.
4. Sodium iodide injection finds use in diagnosis of proper functioning of thyroid gland.
5. Sodium iodohippurate injection finds use in the study of renal function.
6. Sodium rose Bengal injection finds use as diagnostic agent to test liver function.
3. In research:
Excellent biological and medicinal studies have been carried out with radioactive isotopes as
tracers
4. Sterilization:

✓ Excellent use is being made of the radiation constantly available from some strong radiation
source for sterilizing pharmaceuticals in their final packed containers and surgical
instruments in hospitals.
✓ Thermolabile substances like vitamins, hormones antibiotics can be safely sterilized.
✓ Finds use in sterilization of pharmaceuticals.
Measurement of Radioactivity:
➢ To measure the radiations of alpha, beta and gamma particles, many
techniques involving detection and counting of individual particles or
photons are used.
Gas ionization devices:
✓Ionization chambers
✓Proportional Counter
✓Geiger Muller Counter
✓Scintillation Counter
1) IonisationChambers:
❖They are available in various shapes and sizes.
❖An ionization chamber consists of a chambers filled with gas and fitted with two electrodes
kept at different electrical potentials and a measuring device to indicate the flow of electric
current
❖Radiation brings about ionization of gas molecules or ions which cause emission of
electrons which in turn reveals the changes in electrical potential.
2) Proportional counters:
❖ They are modified ionization chambers in which an applied potential ionization of primary
electrons causes production of more free electrons which gets carried to the anode.

❖ For each primary electron liberated, much more additional electrons get liberated, the
current pulse through electrical circuit is greatly amplified.

❖ The voltage range over which the gas amplification (ionization) occurs is called the
proportional region, and the counters working in this region are called Proportional
counters.
3) Geiger-Muller Counter:
➢ These are most popular radiation detectors.
➢ They do not need the use of high gain amplifier.
➢ They can detect alpha, beta and gamma radiations.

➢ Geiger-Muller counter is having ionizing gas and is also having a quenching (decreases the
fluorescence intensity of a given substance) vapour whose functions are:
1. To prevent the spurious pulses that may get produced due to the positive ions (cations)
reaching the cathode (- electrode).
2. To absorb the photons emitted by excited atoms and molecules returning to their ground
state.

➢ Chlorine and bromine are generally used as quenching agent.

➢ Ethyl alcohol and ethyl formate are used as organic quenching agents.
➢ The filling gas pressure has been much below the atmospheric pressure to avoid use of high
operating voltages.
Construction:
❑ A GM Counter possesses a cylindrical cathode (- electrode) , which is usually 1-2 cm in
diameter, along the centre of which is a wire-anode (+ electrode) .
❑ The space is filled with a special gas mixture which gets readily ionized together,
with a small proportion of quenching vapour.
✓ In order to count the medium and high energy beta particles and for gamma counting, thin
glass walled counters may be used.
✓ They are normally 1 cm in diameter and having a glass wall of 20 – 40 mg cm-2 thickness.
❑Operation:
✓ When ionizing radiation such as alpha, beta or gamma particle enters the tube, it can ionize
some of the gas molecules in the tube.
✓ From these ionized atoms, an electron is knocked out of the atom and so the remaining atom
is positively charged.
✓ The high voltage in the tube produces an electric field inside the tube.
✓ The electrons that were knocked out of the atom are attracted to the positive electrode
(anode) and the positively charged ions are attracted to the negative electrode (cathode)
✓ This produces a pulse of current in the wires connecting the electrodes an this pulse is
counted.
✓ After the pulse is counted, the charged ions become neutralized and the Geiger counter is
ready to record another pulse.
✓ For proper use of the Geiger counter, one must have appropriate voltage across the
electrodes.
✓ If the voltage is too low, the electric field in the tube is too weak to cause a current pulse. If
the voltage is too high, the tube will undergo continuous discharge and it will be damaged.
✓ For low voltages, no counts are recorded. This is because the electric field is too weak for
even one pulse to be recorded.
✓ The voltage at which the GM tube just begins to count is called the stating potential. The
counting rate quickly rises as the voltage is increased.
✓ The rise is so fast that the graph looks like a step potential.
✓ After the quick rise, the counting rate levels 0. This range of voltages is termed as pleateau
region.

✓ Eventually the voltage becomes too high and we have continuous discharge.
✓ The threshold voltage is the voltage where the plateau region begins. Proper operation is
when the voltage is in the plateau region of the curve.
✓ For best operation, voltage should be selected fairly close to the threshold voltage.
Geiger Plateau:
4) Scintillation counters: (For gamma counting)
✓ When radiation is incident on certain substances such as phosphor, a flash of light is given
out.
✓ It thus becomes possible to measure alpha, beta and gamma radiations by scintillation
detectors provided the detector has been suitably modified for the type of radiation to be
measured.
✓ The scintillation counter consists of a cell, a photomultiplier tube which is coupled with
phosphor or fluorescent material to convert scintillation into electrical pulses, amplifier.
✓ Crystals of certain substances e.g. cesium fluoride, cadmium tungstate, anthracine and
sodium iodide emit small flashes of light when bombarded by γ-rays.
✓ The most commonly used phosphor in scintillation counters is NaI with a minute quantity of
thallium added.
✓ In the instrument, the crystal is positioned against a photocell which in turn is linked to a
recording unit.
✓ The number of flashes produced per unit time is proportional to the intensity of radiation.
Scintillation counters: