Introduction to radiopharmaceuticals

On the completion of this chapter,

the students should be able to 
Define radioactivity and types of radiation. 
Name units of measurement of radioactivity. 
Identify key radiation safety health hazards. 
Identify types of applications of different types of radioactive compounds. 
Identify salient elements in the formulation and dispensing of radiopharmaceuticals. 
Calculate activity and dose of a radioactive material

By definition, a radiopharmaceutical is a radioactive pharmaceutical agent that is used for

diagnostic or therapeutic procedures
Radiopharmaceuticals, drugs whose molecular makeup includes a radioactive isotope, they are
extremely important in the diagnosis and treatment of disease
Radioisotopes are extensively used in nuclear medicine 
-to allow physicians to explore bodily structures and functions in vivo
Radioisotopes are also used in radiotherapy (radiation therapy) 
-to treat some cancers and other medical conditions that require destruction of harmful cells
Radioisotopes
Atomic number (Z)
Mass number (A)
Nuclides : is a nuclear spp x.rized by the magnitudes of its atomic and mass number.
Isotopes : Atoms of a given element which differs in atomic mass but which have the same
nuclear charge (atomic number
Stable and unstable Isotopes
 Nuclei of an isotopes which contain fewer or more neutrons than protons may be Unstable.
An isotope with unstable nuclei is known as a radioisotopes.
 Examples: Carbon 12C ,13C stable nuclides
10C 14C Unstable
Sodium 23Na stable nuclides
24Na Unstable
Radioactive decay
Any radionuclide tends to change in to a more stable configuration by the process known as
Radioactive decay.
In order to assume a stable state, an orbital electron and lose its excess energy or lose a charged
particle.
The charged particle and the energy emitted by a nucleus undergoing transformation are termed
Nuclear radiation. 
The resulting nucleus has a lower energy content than that of its parent ( radioactive) nucleus. 
The radionuclide disintegrates by first order kinetics  Radioactive decay is the spontaneous
breakdown of an atomic nucleus resulting in the release of energy and matter from the nucleus
When the atomic nucleus undergoes spontaneous transformation, called radioactive decay, radiation is
emitted
If the daughter nucleus is stable, this spontaneous transformation ends 
If the daughter is unstable, the process continues until a stable nuclide is reached
Most radionuclides decay in one or more of the following ways:  Alpha decay 
-beta-minus emission,beta-plus (positron) emission 
-Gamma radiation
Clinical use of radiopharmaceuticals

1. Radiopharmaceuticals for diagnostic purpose.

- Are used to obtain information about the patient (structure and function) 
-When radiopharmaceuticals are used for diagnostic purposes minute quantities are used 
-The radiopharmaceutical accumulates in target tissues and emits gamma-radiation that can be
detected by imaging instruments
.a)Static imaging procedures
  Provide essentially structural information 
The camera builds up an image from the patients from which radiation is emitted; this image is
enhanced by a computer.
Some types function by being concentrated only in the normal tissue of the organ, in which case the
diseased tissue appear on the image as an area of reduced activity (‘cold’ area).
Other types become concentrated selectively in the diseased tissue with appears on the image as an
area of increased activity (‘hot’ area).
B)Dynamic imaging procedures
Provide information about the function of an organ by demonstrating the way in which a
radiopharmaceutical is handled by the organ over a period of time. 
For example - Brain imaging; under normal circumstances RP do not cross the BBB and the brain
appears to be ‘cold’ when there is cerebral pathology capillaries which are more permeable than
normal.
2.Radiopharmaceuticals for therapeutic purpose
The intention with therapeutic PR is use radiation emitted to damage selectively specific tissues
within the body. 
Example: To kill neoplastic cell 
Thus, it is important that the RP localizes in the required part of the body and the radiation emitted
achieves the desired result.
requires higher dosages of alpha-or betaemitting radiopharmaceutical
Formulation of Radiopharmaceuticals
Preparation of RP for clinical administration necessitates several considerations
1.Sterility 
2.Pyrogens and endotoxin limit 
3.Adsorption of the radiopharmaceutical to the container
Radiation safety
Radiation exposure can lead to several side effects 
commonly observed radiation effect 
Hair loss 
Gastrointestinal irritation becoming evident as nausea, vomiting, 
diarrhea, and stomach upset 
Low white blood cell count (leucopenia) (Survivors in Hiroshima and Nagasaki) 
Local side effects such as reddening and itchiness of the skin, if applied 
Oral mucositis, leading to sore mouth or oral ulcers
Generally, doses higher than 30 μCi are administered in a hospital setting to ensure adequate safety
monitoring 
Avoiding unintended exposure to radiation should be done by through careful: 
inventory control 
engineering controls when handling radioactive materials (such as the use of fume hoods) 
proper storage and disposal of radioactive material and contaminated waste.
The following protection guidelines are recommended 
1.Time: 
-quick and efficient work with minimal time of exposure 
-Minimize the time spent handling the radioactive material. 
2.Distance: 
-Maintenance of as long a distance as possible between the finger and the radioactive
source.
3.Shielding: 
-handled in lead containers (shielding material), since lead absorbs and is impervious to all
radiation
Storage & Waste disposal of RP
-RP should be stored at lower temperature in separate store steel locker with lead container 
-Useful precaution includes: 
-Separation of liquid and solid wastes 
-Storage of the waste for each isotope separately or mixed only with waste from other isotopes of
about the same half-life
-Labelling of waste containers with contents,date and radiation level.
-Storage in a special area 
-Waste is not poured down the sink, incinerated,or put in to the public health service refuse bin

Pharmaceutical Incompatibility
Incompatibility may be defined as mixing two or more antagonistic substances resulting in an
undesirable product, which may affect the safety,efficacy and appearance of the preparation.
An incompatibility occurs
when one drug is mixed with other drugs or agents, producing resulting in an undesirable product,
which may affect the safety,efficacy and appearance of the preparation.

There are three types of incompatibilities:

1.Physical incompatibilities
2.Chemical incompatibilities
3.Therapeutic incompatibilities
Physical incompatibilities: When two or more antagonistic substances are combined together, a
physical change takes place and an unacceptable product is formed due to immiscibility,insolubility or
liquefaction. The changes are visible and can be corrected by an application of pharmaceutical skill to
obtain a product of a uniform dosage and an attractive appearance.
 A physical change takes place and an unacceptable product is formed
due to:
-immiscibility
-Insolubility/precipitation
-Liquefaction
-Adsorption to excipient or containers
-Complex formation
The changes are visible and can be corrected by an application of
pharmaceutical skill.
1. Immiscibility
Example: Castor oil
Water (q.s.) 100 ml
Incompatibility: Oil and water do not mix.
Remedy: Carry out emulsification by the addition of an emulsifying
agent,by the use of primary emulsion formula
2. Insolubility
Example: Phenacetin 3.33g
Caffeine 1.1 g
Orange syrup 13.3ml
Water (q.s.) 100ml
Incompatibility: Phenacetin is an indiffusible solid.
Remedy: Compound powder of tragacanth (2 g/100 ml of finished product) or tragacanth
mucilage is used as a suspending agent.
It increases the viscosity of the preparation and helps to maintain a uniform distribution of the insoluble
substances for sufficiently long time after shaking the bottle in order to facilitate removal of a uniform
dose.
3. Liquefaction
Example: Menthol 130 mg
Camphor 260 mg
Light magnesium oxide 390 mg
Incompatibility: When two organic substances having a low melting point are brought
into physical contact with each other, they liquefy due to the formation of a new substance that has a
melting point below room temperature.The reason for this change is that each ingredient acts as an
impurity for the other, thereby lowering their melting point. Such substances are called eutectic
substances.
Example:Menthol, camphor, thymol and ammonium chloride
Remedy: Eutectic powders may be dispensed in following two ways:
(a) They can be dispensed as a separate set of powders with directions that one set of each powder
may be taken as a single dose.
(b) They can also be dispensed by adding a high melting point inert substance such as kaolin, starch,
lactose or light magnesium oxide. These substances act as adsorbents and prevent liquefaction.

2. Chemical incompatibilities: These are caused by pH changes, complex formation, oxidation–

reduction, hydrolysis or combination reactions. These reactions are noticed by precipitation,
effervescence, decomposition, color change or explosion
Alkaloidal salts with alkaline substances:
- Alkaloids are weak bases which are slightly soluble or insoluble in water but alkaloidal salts are
soluble in water.
- If these salts are dispensed with alkaline preparations such as strong ammonia solution or ammonium
bicarbonate, the free alkaloid may be precipitated out.
Example: Strychnine hydrochloride solution………. 5 ml
Aromatic spirit of ammonia ………………3.332 ml
Water (q.s.)……………………………….. 100 ml
Incompatibility: Strychnine hydrochloride is an alkaloidal salt, whereas aromatic
spirit of ammonia is an alkaline substance.
-When they both react, strychnine gets precipitated
Remedy:Divide the vehicle into two portions.
 : The reactants are dissolved in separate portions and mixed slowly by adding one to the other
with rapid stirring.
 :The formed diffusible precipitates are uniformly dispersible with mild shaking of the contents

 Others examples of chemical incompatibility

 -Alkaloidal salts with salicylates
 - Soluble salicylates with alkali bicarbonates
-Soluble salicylates and benzoates with acids
 - Incompatibility leading to evolution of CO2
-Herapathite reaction (quinine sulfate with iodides)

3. Therapeutic incompatibilities: These may be as a result of prescribing certain drugs to a

patient with an intention to produce a specific degree of pharmacological action, but the nature or
intensity of action produced is different from that intended by the prescriber.
 Therapeutic incompatibility arises as a result of prescribing certain categories of drugs to patients
with a sole intention of achieving a specific degree of pharmacological action.
 However, the nature or intensity of the resultant activity is quite different from that intended by the
prescriber.
-Therapeutic incompatibility results due to the following reasons:
 - Error in dosage form
-Wrong dose or dosage form
-Contraindicated drugs
-Synergistic and antagonistic drugs
-Drug interactions
-Prescribing drugs with wrong direction

Veterinary dosage forms