Radiopharmaceuticals

Question 1

What is Radiopharmacy?

Answer 1

Science and art of the design, preparation, quality assurance and clinical practice of radioactive medicines

Question 2

What are Radiopharmaceuticals?

What are the Routes of Administration?

Answer 2

• Any medicinal product which when ready for use, contains one or more radionuclides included for a medicinal purpose (either diagnostic or therapeutic)
• They may be administered
  
  • IV
  • Oral

Question 3

What are the Characteristics of Radiopharmaceuticals?

• Incorporates?
• Used for?
• Pharmacologic Effects?
• Inherent Characteristic?
• Radioactivity expressed in?
• Activities used in radiopharmacy are in the range of what?

Answer 3

• A pharmaceutical, incoporates one or more radionuclides
• Used for diagnosis or therapy
• Usually have no pharmacologic effects since they’re used in tracer quantities
• Inherent Characteristic = Radiation
• Radioactivity is expressed in Bq as the SI Unit
• Activities used in radio pharmacy are in the range of MBq or GBq

Question 4

How do Radiopharmaceuticals work to treat or to be used as diagnostic tools?

Answer 4

• Diagnostic
  
  • Act as signal
  • Accumulate at certain site
  • Give off radiation and the radiation is then captured by whatever mechanism being used
• Treat
  
  • Radiation must act specifically at the site that it’s meant to be working
  • Not meant to be generalised as cells will die unecessarily

Question 5

What do each of the components stand for?

Answer 5

• 2 = atomic number, proton number: number of protons in nucleus
• He = element
• 4.003 = atomic mass: number of protons and neutrons within the nucleus

Question 6

Why do isotopes exist?

Answer 6

• Isotopes exist when there is a large difference between protons and neutrons
• Have excess amount of energy which is given out as radiation
• It will then form a stable atom

Question 7

What is Radiation?

Answer 7

Process of Emission of Energy in the form of particulate radiation or electromagnetic radiation

Question 8

What are the types of Particulate Radiation?

Answer 8

• Alpha decay
• Beta minus decay
• Beta plus decay

Question 9

What is the Type of Electromagnetic Radiation?

Answer 9

Gamma Decay

Question 10

What is Isomeric Transition?

Answer 10

• Isomers are nuclides with the same atomic mass number and atomic number but one of the isomers is in an excited state called the metastable stable
• This results in two different energy levels

Question 11

What is the Penetration Potential of Alpha?

Answer 11

• Energy very high
• Short range
• Stopped by a piece of paper
• Can cause severe cell death but also very effective cell death

Question 12

What is the Penetration Potential of Beta?

Answer 12

• Stopped by aluminum or plastic
• Ingesting can cause a lot of problems

Question 13

What is the Penetration Potential of Gamma?

Answer 13

• Used for diagnostic purposes
• Extensive penetration

Question 14

What is the difference between Alpha and Beta Particles?

Answer 14

• Alpha
  
  • High linear energy transfer
  • Relatively short range
  • Can cause extensive damage in small area
• Beta
  
  • Low linear energy transfer
  • Relatively long range
  • Can cause extensive damage in large area

Question 15

How do Diagnostic Radiopharmaceuticals work?

Answer 15

• Act as signal generator usually not given in large quantities
• Once ingested, starts to accumulate and give off signals, detected by detecting mechanism
• Short exposure for patient
• Usually given by IV and freshly prepared due to shorter t1/2 life

Question 16

What do Diagnostic Radiopharmaceuticals emit?

What must it do before being detected?

What are the most common types of isotopes for imaging?

Answer 16

• Usually these are isotopes that emit penetrating gamma rays
• Radiation has to escape from the body before it can be detected by a specific device
• Most common types of isotopes are: 99mTc, I-123, I-131, Ti-201, In-111

Question 17

How are Diagnostic Radiopharmaceuticals used in the Brain?

Answer 17

• Technetium-99m Bicisate Inj
• Used in diagnosis of Stroke
• Technetium-99m Bicisate forms a stable, lipophilic complex that crosses the BBB by passive diffusion
• Once in the brain cell, the parent compound is metabolised to polar, less diffusible compounds
• Brain images can be obtained from 10 min to 6 hrs post injection

Question 18

How are Diagnostic Radiopharmaceuticals used in the Bone?

Answer 18

• Sodium Oxidronate for the prep of Technetium-99m Oxidronate inj
• Used to capture 2D images of bone, especially identify areas of altered osteogenesis as it accumulates in the mineral part of bones
• Upon IV inj, Technetium Oxidronate is rapidly taken up in the skeleton
• Imaging of the skeleton can start 2-4 hrs post injection

Question 19

How are Diagnostic Radiopharmaceuticals used in the Heart?

Answer 19

• Thallous-201 Chloride Inj
• Used in imaging of myocardial perfusion
• Uptake in the myocytes via K-uptake mechanisms
• Transport of Thallium is 10 times more efficient compared to K
• Images can be obtained from the start of IV inj to about 30 min with patient doing a bit of exercise

Question 20

How are Diagnostic Radiopharmaceuticals used Renally?

Answer 20

• Chromium-51 Edetate Inj
• Used to determine GFR
• Within 30-90 min after IV inj, drug equilibrates between intra- and extravascular spaces
• Kidneys then excrete a constant amount over time

Question 21

What are the 2 Ways Therapeutic Radiopharmaceuticals work?

Answer 21

• Direct
  
  • Beta particles and alpha particles act directly on the DNA of the cell
  • The energy causes breaks in DNA and can’t be repaired leading to cell death
• Indirect
  
  • X-ray and gamma radiation
  • Energy reacts with water causing the water to radiolyse and form free radicals of H- with H+
  • These ions can further react with oxygen to form superoxides and peroxides causing molecules to become damaged and causes cell death

Question 22

What are the 3 types of treatment in therapeutic radiopharmaceuticals?

Answer 22

1. Molecular-mediated treatment
2. Monoclonal-mediated treatment
3. Small molecule-mediated treatment

Question 23

What is a type of Molecular-mediated treatment in Radiopharmaceuticals?

Answer 23

• Radium 223 in prostate cancer with bone metastases
• Radium 223 is a calcium mimetic and is actively incoporated into bone matrix and delivers ionising radiation to areas of increased osteoblastic activity

Question 24

What is a type of Monoclonal-Mediated treatment in Radiopharmaceuticals?

Answer 24

• Radio labelled antibodies:
  
  • Recognise and interact with specific antigens
  • Example: Iodine-131 Tositumomab

Question 25

What are Radio labelled peptides used for in Radiopharmaceuticals?

Answer 25

* Radio isotope attached to a peptide analogue, recognised by receptor of the cell * It's taken up by the body * Radio isotope released and brings about cell death

Question 26

Discuss the use of Actinium 225 against prostate specific membrane antigen 617

Answer 26

Whatever prostate cancerous cells express this antigen 617, this molecule will target those cells and will be taken up by those cells and then it will kill those cells

Question 27

Discuss the Formulation of Radiopharmaceuticals * How are they administered? * What is a challenge? * How are they prepared?

Answer 27

* Most are administered by IV injections * Challenge is to prepare them as sterile and apyrogenic prep while working against the physical half life of the radionuclide and dealing with radiation issues * Many are prepared as 'kits'

Question 28

List the main components in Radiopharmaceuticals

Answer 28

* Active ingredient * Reducing agent * Antioxidant stabiliser * Inert air atmosphere * Buffer * Others e.g. solubilising agent, buling agent and bacteriostat

Question 29

Main components in Radiopharmaceuticals: What is the role of the Active?

Answer 29

* Not radioactive material * The radioactive material is either attached or react with the active so that you'll form a complex which is what's taken up by the body

Question 30

Main components in Radiopharmaceuticals: What is the role of the Reducing Agent?

Answer 30

* To make sure Radioactive material is in particular oxidative state and is able to react with active ingredient to form complex

Question 31

Main components in Radiopharmaceuticals: What is the role of the Antioxidant Stabiliser and Inert air atmosphere?

Answer 31

* Remove any oxidants in air or formulation itself so that the radioactive material doesn't change oxidative state

Question 32

Main components in Radiopharmaceuticals: What is the role of the Buffer?

Answer 32

To make sure pH is maintained

Question 33

Main components in Radiopharmaceuticals: What is the role of the Solubilising Agent?

Answer 33

To make sure everything you add has been completely dissolved

Question 34

Main components in Radiopharmaceuticals: What is the role of the Bulking Agent?

Answer 34

To make sure you see a 'plug'

Question 35

What are there strict regulations in place for?

Answer 35

* Design of Pharmacy * Production * Packaging * Labelling * Transportation * Dispensing

Question 36

The label on the Primary Container should include?

Answer 36

* A statement that the product is radiactive or the international symbol for radioactivity * Name of the radiopharmaceutical preparation * Diagnostic or for therapeutic use * Route of administration * The total radioactivity present at a stated date * Expiry and time if necessary * Batch number * Total volume for solutions