RADIOPHARMACEUTICALS

Definition

Radiopharmaceuticals are the radioactive substances or radioactive drugs used for diagnostic or

therapeutic interventions.

Radiopharmaceuticals are medicinal formulations containing radioisotopes which are safe for

administration in humans for diagnosis or for therapy.

Composition

• a radioactive isotope that can be injected safely into the body, and

• a carrier molecule which delivers the isotope to the area to be treated or examined

Principle

• Unstable or radioactive isotopes have a property to decompose or decay by emission of

nuclear particles and some of them are used in diagnostic or therapeutic interventions.

• The three main types of radiation decay are α particles, β particles, γ photons.

• α particles have the largest mass. However, due to large charge, it does cause a great deal

of damage to the immediate area by breaking down DNA.

• β particles are electrons. β particles are not as destructive as α particles but can be used

therapeutically.

• γ rays are electron magnetic vibrations comparable with light but of shorter wavelength.

Because of their shorter wavelength and high energy, they are very penetrating.
APPLICATIONS / USES OF RADIOPHARMACEUTICALS

• Diagnosing

• Therapeutic

Radio-Imagining

SPECT vs PET

 In SPECT (Single Photon Emission Tomography), the emitted radiation already is a

Gamma ray, which is then directly used to create the camera images. SPECT cameras

use collimators to help localizing with precision the direction of the incoming ray.

 In PET (Positron Emission Tomography), the emitted radiation is a positron which, when

interacting with the tissues around the radiopharmaceutical, creates 2 rays, one opposite

the other. The rays hit a camera and the two signals taken in coincidence allow a

 precise localization of the emission point.

Difference Between SPECT and PET

SPECT PET
 Emits gamma radiations  Emits positrons
 More than one detector around the patient  Ring of detectors
 Poor resolution  Good resolution
 Low sensitivities  High sensitivity
 Less capital-intensive scanner  Costlier scanner
 Longer lived radioisotopes  Shorter lived radioisotopes
Mechanism of Action

 Diagnostic Radiopharmaceuticals: these agents emit gamma radiation, which is detected

by imaging equipment. They are usually injected into the patients’ bloodstream and

accumulate in specific organs or tissues allowing visualization and assessment of their

function.

 Therapeutic Radiopharmaceuticals: These agents emit radiation that is targeted to destroy

or inhibit the growth of specific diseased cells or tissues. They are administered in higher

doses compared to diagnostic radiopharmaceuticals

Applications

 Diagnostic Applications: detection and localization of tomours, assessment of organ

function, evaluation of blood flow and metabolism, detections and evaluation of bone

health.

 Therapeutic Applications: Treatment of various cancers, thyroids disorders and other

medical conditions.

Diagnostic uses

• Radiopharmaceuticals are used to diagnose the presence of disease or evaluate the

progression of disease following a specific therapy intervention. Radiopharmaceuticals

can also be used to evaluate drug induced toxicity and to a lesser extent have been used to

treat diseased tissue with radiation.

• For example, to analyse thyroid function, a tracer dose of radioactive iodine is

administered orally; the agent concentrates in the thyroid gland. The thyroid is then
 scanned to determine radioiodine concentration and location. Greater than normal up-take

by the thyroid indicates hyperthyroidism.

Therapeutic uses

• Radioisotopes are used as internal or external radiation sources to treat disorders such as

hyperthyroidism and cancer.

i. Internal radiation source- A radioisotope administered orally or intravenously or

implanted in the target tissue or organ will produce radiation that destroys diseased cells

and prevents new tissue growth.

ii. External radiation source- Radiation may be used for therapy in cancer patients.

Uses of Radipharmaceutical in Different Organ Systems

• Pulmonary system: Radioisotope are commonly used in lung perfusion scans, which

help to detect acute pulmonary embolism, and ventilation scans, which helps to

differentiate pulmonary embolism from chronic obstructive pulmonary disease (COPD).

 Eg: Xenon 133 (133Xe) gas– In a ventilation scan, this gas may be administered via

spirometer or a special breathing apparatus to distribute with respiratory air. A decreased

uptake of radioisotope during a perfusion scan indicates a problem with blood flow,

including occlusion of pulmonary artery.

 Skeletal system: Nuclear bone scans are particularly valuable for detecting cancer
99m
metastases, which appear as areas of increased radionuclide phosphate uptake. Tc

methylene diphosphonate may be used in skeletal system.

  Hepatobiliary system: The introduction of radioactive colloids has made possible both

liver visualization and functional evaluation of reticulo-endothelial cells. The use of

radiopharmaceutical reactive dyes permits visualization of the liver and biliary duct and

assessment of hepatocyte function. Example: Iodine 131 (131I) sodium rose bengal.

 Renal system: Radiopharmaceuticals allow both static and dynamic evaluation of the

kidneys.

 Nervous system: Nerve brain scans serve two main purposes: To evaluate changes in

the blood brain barrier and to assess cerebral blood flow.

 Cardiovascular system: Nuclear imaging studies of the heart may be static or dynamic.

A static scan localizes the site of myocardial infarction and analyses myocardial

perfusion. A dynamic study evaluates cardiac function.

Miscellaneous agents:

• Sodium iodide 123 (Na123I): This is the preferred radioisotope in thyroid function studies

and imaging studies of the thyroid, liver, brain and lung.

• Gallium citrate 67 (67Ga): This agent helps to localize tumours and infections of soft

tissues and bone (eg, lymphoma, hepatoma).

Nuclear Pharmacy

• It’s a relatively newer branch of pharmacy that involve the procurement, compounding,

dispensing and quality control of radioactive pharmaceuticals intended to be used for

investigation or treatment of some diseases in humans or animals.

Role of Radio pharmacist

• The radio pharmacist’s main responsibility is the procurement, preparation, quality

control and supply of radio-pharmaceuticals.

• Radio pharmacists also have a clinical role to play. E.g. providing advice on the use of

radiopharmaceuticals and having input to patient care in the nuclear medicine

department. In addition, they may provide education and training to their own staff as

well as other health care professions. There is a scope to get involved in the research and

development of new radio- pharmaceuticals including clinical trials.

Procurement of Radiopharmaceuticals

• Because of the short life of the radiopharmaceuticals the nuclear pharmacist will order

the drug directly from manufacturer usually through overnight delivery. Isotope storage

areas should be as per the rules.

• There should be a separate lab for the manipulation and preparation of radio

pharmaceutical dosage and another for calibration of doses.

Preparation of the radio pharmaceutical

• Formulation of radio pharmaceuticals is more complex than normal pharmaceuticals.

Good Radiation Practices (GRPs) and Good Manufacturing Practices (GMPs) should be

strictly followed during manufacturing and dispensing operations.

Quality Assurance

• Radiopharmaceuticals are generally expected to conform to specifications under the

following heading:
 Radionuclide concentration
 Radiochemical purity
 Sterility
 Apyrogenicity
 Absence of foreign particulate matter
 Particle size (if appropriate)
 pH
Packaging of radio pharmaceutical

• The most effective way to reduce the risk associated with transporting radioactive

materials is to follow the appropriate packaging standards specified by DOT and, when

required, NRC or DOE regulations.

• Three types of containers.

1. Industrial packaging

2. Type A packaging

3. Type B packaging
Industrial Packaging: Materials that present little hazard from radiation exposure, due to their

low level of radioactivity, are shipped in industrial packages.

• Type A Packages: Radioactive materials with higher specific activity levels are shipped

in Type A packages. Typically, Type A packages are used to transport

radiopharmaceuticals (radioactive materials for medical use) and certain regulatory

qualified industrial products.

 • Type B Packages: Radioactive materials that exceed the limit of type A packages

requirements must be shipped in type B packages. These packages are used to transport

materials with high levels of radioactivity such as nuclear power plant, spent fuel.

Labelling of Radioactive Substances

• Every radiopharmaceutical preparation must comply with the labelling requirements

established under Good Manufacturing Practice.

The label on the primary container should include:

• A statement that the product is radioactive or the international symbol for radioactivity

• The name of the radiopharmaceutical preparation

• The route of administration;

• The expiry date and, where necessary, time;

 • The batch (lot) number assigned by the manufacturer;

• For solutions, the total volume.

The label on the outer package should include:

• A statement that the product is radioactive or the international symbol for radioactivity

• The name of the radiopharmaceutical preparation;

• Where appropriate, that the preparation is for diagnostic or for therapeutic use;

• The route of administration;

• The expiry date and, where necessary, time;

• The batch (lot) number assigned by the manufacturer;

• For solutions, the total volume;

• Any special storage requirements with respect to temperature and light;

Storage of Radioactive Substances

 • Radiopharmaceuticals should be kept in well-closed containers and stored in an area

assigned for the purpose.

• Care should be taken to comply with national regulations for protection against ionizing

radiation.

Dispensing of Radiopharmaceuticals

• The dispensing of radio pharmaceuticals should be safe, reliable and straight forward.

• Make sure the recommended dose is based on the patient history, weight of the

patient, body surface area and other factors

• Develops policies and procedures to ensure that correct drug with correct dosage and

dosage form are received by the correct patient at the correct time via route of

administration.

Precautions For Handling Radioactive Substances

The radioactive substances used should comply with the following characteristics:

• Radio toxicity must be as low as possible.

• The amounts used must be kept to a minimum.

• When handling radioactive materials, always wear the appropriate protective clothing

(wear a lab coat, gloves, shoe covers).

• To avoid internal contamination, strict hygiene is essential when handling radioactive

materials

• Wash your hands thoroughly when you leave the lab.

• Never pipette by mouth. Use pipetting devices instead.

• Regularly check the radiation level of your working area and all objects used, or at least

at the end of each working day.

• Dispose of all radioactive waste in the appropriate containers.